Noninvasive measurement system

ABSTRACT

The noninvasive measurement system provides a technique for manipulating wave data. In particular, wave data reflected from a biological entity is received, and the reflected wave data is correlated to a substance in the biological entity. The wave data may comprise light waves, and the biological entity may comprise a human being or blood. Additionally, a substance may comprise, for example, a molecule or ionic substance. The molecule may be, for example, a glucose molecule. 
     Furthermore, the wave data is used to form a matrix of pixels with the received wave data. The matrix of pixels may be modified by techniques of masking, stretching, or removing hot spots. 
     Then, the pixels may be integrated to obtain an integration value that is correlated to a glucose level. The correlation process may use a lookup table, which may be calibrated to a particular biological entity. Moreover, an amplitude and phase angle may be calculated for the reflected wave data and used to identify a glucose level in the biological entity. Additionally, the reflected wave data may be used to determine glaucoma pressure. 
     The glucose level may be displayed on a monitor attached to the computer. The computer may be a portable, self-contained unit that comprises a data processing system and a wave reflection capture system. On the other hand, the computer may be attached to a network of other computers, wherein the reflected wave data is received by the computer and forwarded to another computer in the network for processing.

RELATED U.S. PATENT DOCUMENTS

This application claims priority from International Application No.PCT/US99/121680, “NONINVASIVE MEASUREMENT OF BLOOD SUGAR BASED ONOPTOELECTRONIC OBSERVATIONS OF THE EYE”, filed on Sep. 17, 1999, byWalter K. Proniewicz and Dale E. Winther, which is incorporated byreference herein and which claims priority to U. S. Provisional PatentApplication 60/100,804, “BLOOD SUGAR MEASUREMENT THROUGH THE EYEBALL”,filed on Sep. 18, 1998, by Walter K. Proniewicz and Dale E. Winther,which is incorporated by reference herein.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates generally to apparatus and systems for makingnoninvasive tests, assessments, or determinations of substances that maybe part of a human being or other biological entity and, moreparticularly, to software implemented apparatus and systems thatnoninvasively test, assess, or determine the concentration, or otherfeatures of molecular or other substances in organic matter or fluids,such as blood, existing in human beings and other biological entities.

2. Description of Related Art

There are a number of instances in which it is necessary, or at leasthighly desirable, to test, assess, or determine the concentration, orother features of molecular or other substances contained in organicmatter or fluids, residing in biological entities, such as human beingsor blood. By way of example only, blood tests are used in a variety ofscientific, medical, and other applications, including a test,assessment, or determination of the level of glucose in the blood ofhuman diabetics. Such a test, assessment, or determination is typicallyaccomplished by an invasive procedure which, especially in the case ofhuman diabetics, may require the drawing of blood samples a number oftimes each day in order to adequately monitor the level of glucose inthe blood of the diabetic (i.e. the concentration of glucose in theblood—commonly called “blood sugar”).

In the case of human diabetics, the invasive procedure typicallyinvolves physically withdrawing blood from the finger tips or ear lobesby using suitable lancing devices or withdrawing blood from veins byusing suitable hypodermic syringes. Once withdrawn, the blood sample isthen deposited within a suitable device which determines the level ofblood glucose with a certain level of accuracy and reliability.Increasingly, such devices have taken the form of hand-held monitorsthat human diabetics use to self-test their level of glucose. Thus,conventionally, the human diabetic withdraws his or her blood by alancing device and deposits the withdrawn blood on an indicator stripthat is inserted into the monitor. The deposited blood is then analyzedand furnishes a reading of the level of glucose in the blood of thehuman diabetic. Correspondingly, there are various scientific andmedical applications for which it may be necessary to invasively test,assess, or determine the blood glucose of even individuals who are notdiabetic.

Needless to say, the use of an invasive procedure to test, assess, ordetermine the level of blood glucose is often painful, uncomfortable,frightening, and overall quite undesirable. One of the named inventorsis a diabetic and is, therefore, all too familiar with thesedisadvantages. This is particularly so in the case of certain of humandiabetics who are young children or are very ill or infirm individualsand who may have collapsed veins or other impediments. Invasivewithdrawal of blood from human diabetics and other individuals alsoposes the risk of infection, unseemly scarring and the associated lossof the sensation of feeling, and the exacerbation of pre-existingchronic conditions or illnesses due to the repeated undesirableexperience of invasively withdrawing blood. In fact, these disadvantagesoften may virtually completely dissuade a number of human diabetics fromadequately testing their level of blood glucose, thereby creating asignificant risk of developing serious or even life-threateningcomplications or even shortening their life span. The aforementioneddisadvantages tend also to be exacerbated by the fact that theaforementioned conventional hand-held monitors tend to be at leastnominally subject to relatively significant errors. In fact, it isrelatively commonplace for two separate monitors to register differinglevels of blood glucose by 15-30 percent or more.

It should, therefore, be appreciated that there exists a definite needfor an apparatus and system that noninvasively, and comparativelyaccurately and reliably tests, assesses, and determines the level ofblood glucose (i.e. the concentration of glucose in the blood) in ahuman being and thereby tends to eliminate or substantially reduce thepain, discomfort, trepidation, and overall undesirability associatedwith testing, assessing, or determining the level of blood glucose.There also exists a concomitant need for an apparatus and system thatnoninvasively, and comparatively accurately and reliably tests,assesses, or determines the concentration of molecular or othersubstances in organic matter or fluids, such as blood, existing in humanbeings and other biological entities.

SUMMARY

The present invention, which addresses these needs, resides in acomputer software implemented system, method, apparatus, and article ofmanufacture that noninvasively tests, measures or otherwise assesses ordetermines one or more features of a molecule or other substance of abiological entity.

In accordance with one embodiment of the invention, wave data ismanipulated. In particular, wave data reflected from a biological entityis received and the reflected wave data is correlated to a substance inthe biological entity. The wave data may comprise light waves, and thebiological entity may comprise a human being or blood. Additionally, asubstance may comprise, for example, a molecule or ionic substance. Themolecule may be, for example, a glucose molecule.

Furthermore, the wave data is used to form a matrix of pixels with thereceived wave data. The matrix of pixels may be modified by techniquesof masking, stretching, or removing hot spots.

Then, the pixels may be integrated to obtain an integration value thatis correlated to a glucose level. The correlation process may use alookup table, which may be calibrated to a particular biological entity.Moreover, an amplitude and phase angle may be calculated for thereflected wave data and used to identify a glucose level in thebiological entity. Additionally, the reflected wave data may be used todetermine glaucoma pressure.

The glucose level may be displayed on a monitor attached to thecomputer. The computer may be a portable, self-contained unit thatcomprises a data processing system and a wave reflection capture system.On the other hand, the computer may be attached to a network of othercomputers, wherein the reflected wave data is received by the computerand forwarded to another computer in the network for processing.

In accordance with another embodiment of the invention, a technique fornoninvasively measuring glucose concentration is provided. Inparticular, light waves reflected from an eye as pixels are received.The pixels are integrated to form an integrated value. Then, theintegrated value is correlated to a glucose level.

The pixels may be processed to identify a center of the eye, tocalculate an average brightness around the pupil of the eye, to equalizethe iris of the eye using the brightness around the pupil as a baseline,to mask the pupil of the eye, and/or to remove hot spots.

In accordance with yet another embodiment of the invention, a techniquefor noninvasively measuring glucose concentration is provided. Inparticular, light waves reflected from a biological entity are received.An amplitude and a phase angle are calculated for the reflected lightwaves. Using the amplitude and phase angle, a glucose level isidentified in the biological entity. The biological entity may comprise,for example, an eye, skin, blood, or a nail bed.

The received light waves form a matrix comprised of pixels. Theamplitude is calculated by summing all of the pixels. The phase angle iscalculated by summing the rows of pixels of the matrix to obtain an xGRUvalue, summing the columns of pixels of the matrix to obtain a yGRUvalue, and calculating a ratio of the xGRU value and the yGRU value. Atrue amplitude is calculated by subtracting a phase angle from asummation of pixels formed by the light waves.

The matrix of pixels may be processed to mask a portion of the matrix orby applying a filter to the reflected light waves. Furthermore,automatic level control is performed to modify the value of the pixelsto obtain an average desired value. Automatic fine tuning is alsoperformed.

Other features and advantages of the present invention should becomemore apparent from the following description of the preferredembodiments, taken in conjunction with the accompanying drawings, whichillustrate, by way of example, principles of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

Referring now to the drawings in which like reference numbers representcorresponding parts throughout:

FIG. 1 is a hardware environment used to implement an embodiment of theinvention;

FIG. 2 is a schematic illustration of the hardware environment of anembodiment of the present invention, and more particularly, illustratesa typical distributed computer system;

FIG. 3 is a schematic diagram, in plan, of a CCD camera assembly used inone embodiment of the invention, and contemplated for adaptation into acommercial unit;

FIG. 4 is a block diagram showing the image input data stream derivedfrom optoelectronic measurements of an eye, using the FIG. 3 cameraassembly in a centralized illumination arrangement;

FIG. 5 is an isometric view of a representative illumination geometry,one of several variations, illustrating a diffuse-illumination approach;

FIG. 6 is a perspective view of an optical bench, particularly includinga foam ocular and a forehead rest;

FIG. 7 is a more detailed view shown in FIG. 6;

FIG. 8 is a perspective view of an early eye-tracking system;

FIG. 9 is a perspective view of an early bezel for mounting at the frontof the camera lens and for aiming a small light source toward the eye;

FIG. 10 is an enlarged view of the FIG. 9 bezel, shown with light sourceand eye, in longitudinal elevation generally along the systemcenterline;

FIG. 11 is an illustration of part of a representative control panel,seen on a computer screen while the system is imaging a subject eye andshowing false light images;

FIG. 12 are representative histograms that are another part of the samecontrol panel display, particularly showing histograms representingresults of different processing stages within the program;

FIG. 13 is a display of a control panel associated with an averageprogram and having controls used to correlate typical values with anactual concentration of patient blood glucose in conventional units;

FIG. 14 is a diagrammatic showing of focal-distance measurements thatcan be used to determine glaucoma pressure automatically with apparatusanalogous to certain forms of the glucose-concentration measuringsystems described herein;

FIG. 15 is a flow diagram illustrating the steps performed by thenoninvasive measurement system in one embodiment of the invention;

FIG. 16 illustrates a control panel for one embodiment of the invention;

FIG. 17 displays another control panel for one embodiment of theinvention;

FIG. 18 illustrates various Phase/Amplitude lookup tables that have beencalibrated for different settings;

FIG. 19 displays histograms for Image A and Image B; and

FIGS. 20A-20C are a flow diagram illustrating the steps performed by thenoninvasive measurement system in one embodiment of the invention.

DETAILED DESCRIPTION

In the following description, reference is made to the accompanyingdrawings which form a part hereof, and which is shown by way ofillustration specific preferred embodiments in which the invention maybe practiced. The following description of the preferred embodiments,taken in conjunction with the accompanying drawings, illustrates, by wayof example principles of the invention. It is to be understood thatother embodiments may be utilized as structural changes may be madewithout departing from the scope of the present invention.

A. Overview of the Noninvasive Measurement System

The present invention includes a noninvasive measurement system, method,apparatus, and article of manufacture (which will be referred to belowas noninvasive measurement system), which obtains waves in theelectromagnetic spectrum as input. The electromagnetic spectrumcomprises a broad spectrum of wavelengths and frequencies, includingvisible light, infrared and ultraviolet radiation, audio transmissions,and x-rays. In the embodiments of the invention discussed below, focuswill be on light waves (visible and infrared); however, it will beappreciated that the invention encompasses other types of waves thatprovide information appropriate to the processing described below.

The received waves are reflected off of a biological entity (e.g., humanor other animal or a substance from the biological entity). Inparticular, the waves may be reflected off of an eye, skin, a nail, or ablood sample. The waves are received with a wave reflection capturesystem (e.g., a camera). The noninvasive measurement system processesthe received waves and correlates the reflected waves to a substance inthe biological entity. For example, in the embodiments to be describedbelow, the reflected waves are used to determine the concentration ofglucose (i.e., commonly called blood sugar) that is found in the bloodof a human being.

The noninvasive measurement system has numerous advantages andapplications. For example, the noninvasive measurement system may beused to diagnose patients to determine whether they have diabetes. Thenoninvasive measurement system may also be used as a preventive step tomonitor blood glucose levels in an individual who, for example, has ahistory of diabetes in the family. The noninvasive measurement systemmay also be used to monitor diabetics who need their blood glucoselevels checked multiple times a day or multiple times a week, etc. Thenoninvasive measurement system may also be linked with an insulinreleasing system so that, when the noninvasive measurement systemrecognizes that insulin is needed, it can signal the insulin releasingsystem to release insulin. Furthermore, the noninvasive measurementsystem may be used to obtain glaucoma pressure.

The noninvasive measurement system may also be used to locate tumors andto locate and correct blood clots. For example, the noninvasivemeasurement system may be used to detect breast cancer by processinglight that penetrates through flesh and is reflected.

The noninvasive measurement system may process x-rays or other highenergy particles, instead of light waves, with application to varioustechnologies using x-rays and other high energy particles (e.g., medicaltechnologies). Moreover, the noninvasive measurement system may processultraviolet rays to highlight or detect different types of minerals orother substances, such as ethanol present in the blood. The noninvasivemeasurement system can distinguish between substances based on theirrotation (e.g., a glucose molecule rotates in a clock-wise direction asits density increases, while, a fructose molecule rotates in acounter-clockwise direction).

As for advantages, the noninvasive measurement system effectivelyeliminates need for piercing the body or otherwise obtaining bloodsamples, and so avoids the discomfort, fear and other detriments ofusing a conventional one touch glucose monitor. Additionally, thenoninvasive measurement system can be manufactured as a small unit ormonitor that can fit, for example, in the palm of a hand, thus allowingfor use at home, or at an office or other business, or in cars,restaurants, etc.

B. Hardware Environment

In one embodiment, wave input is provided to a computer, which performsthe processing of the input and displays a result on a monitor attachedto the computer. FIG. 1 is hardware environment used to implement anembodiment of the invention. The present invention is typicallyimplemented using a computer 100, which generally includes one or moreprocessors 102, random access memory (RAM) 104, data storage devices 106(e.g., hard, floppy, and/or CD-ROM disk drives, etc.), datacommunications devices 108 (e.g., modems, network interfaces, etc.),display devices 110 (e.g., CRT LCD display. etc.). and input devices 112(e.g., camera, video recorder, mouse pointing device, and keyboard). Itis envisioned that attached to the computer 100 may be other devices,such as read only memory (ROM), a video card, bus interface, printers,etc. Those skilled in the art will recognize that any combination of theabove components, or any number of different components, peripherals,and other devices, may be used with the computer 100.

The computer 100 operates under the control of an operating system (OS)114. The operating system 114 is booted into the memory 104 of thecomputer 100 for execution when the computer 100 is powered-on or reset.In turn, the operating system 114 then controls the execution of one ormore computer programs 116, such as a noninvasive measurement system 118and a counter 120, by the computer 100. The present invention isgenerally implemented in these computer programs 116, which executeunder the control of the operating system 114 and cause the computer 100to perform the desired functions as described herein. Although shown asseparate from the noninvasive measurement system 118, one skilled in theart would recognize that the counter 120 may be part of the noninvasivemeasurement system.

The operating system 114 and computer programs 116 are comprised ofinstructions which, when read and executed by the computer 100, causesthe computer 100 to perform the steps necessary to implement and/or usethe present invention. Generally, the operating system 114 and/orcomputer programs 116 are tangibly embodied in and/or readable from adevice, carrier, or media, such as memory 104, data storage devices 106,and/or data communications devices 108. Under control of the operatingsystem 114, the computer programs 116 may be loaded from the memory 104,data storage devices 106, and/or data communications devices 108 intothe memory 104 of the computer 100 for use during actual operations.

Thus, the present invention may be implemented as a method, apparatus,system, or article of manufacture using standard programming and/orengineering techniques to produce software, firmware, hardware, or anycombination thereof. The term “article of manufacture” (oralternatively, “computer program product”) as used herein is intended toencompass a computer program accessible from any computer-readabledevice, carrier, or media, including the internet. Of course, thoseskilled in the art will recognize many modifications may be made to thisconfiguration without departing from the scope of the present invention.

Those skilled in the art will recognize that the environment illustratedin FIG. 1 is not intended to limit the present invention. Indeed, thoseskilled in the art will recognize that other alternative hardwareenvironments may be used without departing from the scope of the presentinvention. For example, the computer 100 may be a portable,self-contained unit that comprises a data processing system and a wavereflection capture system (e.g., a camera). The computer 100 may beabout the size of the palm of an average individual's hand. Moreover,the noninvasive measurement system 118 may be incorporated intodifferent apparatus than those illustrated herein. Additionally, thecounter 120 may comprise software that is structured to limit the use ofthe noninvasive measurement system over a specified period of time(e.g., one year) or for a specified number of uses (e.g., 1000 uses).

In another embodiment of the invention, wave input is provided to aclient computer, which transmits the data to a server computer foranalysis. FIG. 2 is a schematic illustration of the hardware environmentof an embodiment of the present invention, and more particularly,illustrates a typical distributed computer system using a network 200 toconnect client computers 202 executing client applications to a servercomputer 204 executing software and other computer programs, and toconnect the server system 204 to data sources 206. A typical combinationof resources may include client computers 202 that are personalcomputers or workstations, and a server computer 204 that is a personalcomputer, workstation, minicomputer, or mainframe. These systems arecoupled to one another by various networks, including LANs, WANs, SNAnetworks, and the Internet. Each client computer 202 and the servercomputer 204 additionally comprise an operating system and one or morecomputer programs.

A client computer 202 typically executes a client application and iscoupled to a server computer 204 executing one or more server software.The server software may include a noninvasive measurement system 210.The server computer 204 also uses a data source interface and, possibly,other computer programs, for connecting to the data sources 206. Theclient computer 202 is bi-directionally coupled with the server computer204 over a line or via a wireless system. In turn, the server computer204 is bi-directionally coupled with data sources 206. The data sources206 may be geographically distributed.

The operating system and computer programs are comprised of instructionswhich, when read and executed by the client and server computers 202 and204, cause the client and server computers 202 and 204 to perform thesteps necessary to implement and/or use the present invention.Generally, the operating system and computer programs are tangiblyembodied in and/or readable from a device, carrier, or media, such asmemory, other data storage devices, and/or data communications devices.Under control of the operating system, the computer programs may beloaded from memory, other data storage devices and/or datacommunications devices into the memory of the computer for use duringactual operations.

Thus, the present invention may be implemented as a method, apparatus,system, or article of manufacture using standard programming and/orengineering techniques to produce software, firmware, hardware, or anycombination thereof. The term “article of manufacture” (oralternatively, “computer program product”) as used herein is intended toencompass a computer program accessible from any computer-readabledevice, carrier, or media, including the internet. Of course, thoseskilled in the art will recognize many modifications may be made to thisconfiguration without departing from the scope of the present invention.

In one embodiment, in a networked environment, part or all of thenoninvasive measurement system may reside at the server computer. Anindividual may transmit an image of, for example, their eye at theclient computer to the server computer. The noninvasive measurementsystem would process the image data and return a blood glucose level(i.e., commonly referred to as “blood sugar”) to the client computer,for use by the individual.

Those skilled in the art will recognize that the exemplary environmentillustrated in FIG. 2 is not intended to limit the present invention.Indeed, those skilled in the art will recognize that other alternativehardware environments may be used without departing from the scope ofthe present invention.

C. Noninvasive Measurement of Glucose Concentration in an Eye

The noninvasive measurement system determines the concentration ofglucose in blood, without the need for invasive procedures. Thenoninvasive measurement system can determine glucose levels by analyzinglight waves reflected from the eye.

A handheld illumination and imaging system is used to take blood glucosemeasurements. The system advantageously operates by integrating thereflected light from the-iris portion of the eye, rather than from theretina. Numerous anterior blood vessels present a means of directlyobserving bloodstream content with exterior optical techniques.

Glucose accumulations in this area produce a change in the intensity ofreflected light. The more glucose present, the higher the level ofreflected light. The concentration of glucose in this area canpotentially change in seconds.

This change in light reflection is too small to be seen with normalobservation techniques. The ability to measure light intensity changesas small as 1 part in 10,000 is required to detect blood glucosechanges.

A CCD camera images the eyeball and the image is digitized. These dataare processed to remove the pupil pixels. Only the iris pixels are usedas representative of glucose levels as such, but as explained elsewherethe pupil pixels are used to develop baseline and illumination levels.

The iris pixels are integrated (summed) to produce a single intensitynumber. This is sometimes called the “integrated data number” or IDN forshort; it is interchangeably designated “GLU”, for glucose value.

The IDN (or GLU) value can be calibrated by removing image scene andillumination discrepancies. It can be further calibrated to anindividual patient to produce an extremely accurate IDN-to-blood-glucose(GL or glucose level) correlation. Repeatable scene geometry is alsovery desirable for accurate measurements.

As mentioned above, the primary IDN calibration technique uses pupilreflection and geometry data. Changes in input light levels are detectedby sensing pupil brightness.

The average reflected intensity level of the pupil is used as thedark-level baseline for IDN processing. Only intensities that are higherthan that of the pupil are integrated into the IDN.

This is a scene-to-scene automatic light level calibration. If the scenelight level goes up, so do the levels of the pupil and -iris. The pupillevel offsets the higher iris level and preserves the scene-to-scenerelative brightness. This guarantees that only glucose-level increaseswill cause measured intensity increases.

The following pseudo-code reflects the processing performed by thenoninvasive measurement system. Further details about each of theseprocessing steps will be discussed below.

1. image the eyeball

2. find the center of the pupil

3. calculate the average brightness around the pupil center

4. mask out the pupil region of the eye

5. equalize the iris image using the pupil brightness as a levelbaseline

6. remove hot spots if present

7. integrate all of the processed iris pixels

8. search a lookup table to find the closest IDN-to-GL correlation

9. display the imputed glucose number in GL

C.1 Image the Eyeball

Imaging the eyeball refers to taking a picture of the eye. Inparticular, the noninvasive measurement system transmits broad spectrumvisible and near infrared light to the eye. The transmitted light cancome from different sources, such as tungsten light, light emittingdiodes (LEDs), and white or colored light bulbs.

The noninvasive measurement system receives back a portion of the waves(i.e., some of the waves are absorbed). In one embodiment, the portionreceived back and used comprises' infrared waves. As blood glucosechanges, the amount of reflected light changes. This is believed to bedue to the fact that glucose is a substance that reflects light and thatmay increase. On the other hand, blood absorbs light. Therefore, asglucose increases in the blood, more light is reflected from the glucosesubstance, and less is absorbed by the blood.

The noninvasive measurement system comprises an apparatus that holds alight source directly in front of the camera lens. The light source ismade to shine onto the eye from the geometric center of the camera lens.This results in even illumination of the eye, eliminating reflectionsand hot spots.

Two additional effects are created by this central-illuminationgeometry:

-   -   1. the light source becomes a visual centering target for the        patient; and    -   2. the light source becomes a peak amplitude point for finding        the image center.

After transmitting light toward the eye, the noninvasive measurementsystem takes a picture of the eye. This results in the light waves thatare reflected from the eye passing through a lens system. The lensfocuses the waves on the surface of a CCD detector. The waves strikewith different amounts of energy and different angles. This leads to apicture that is represented by pixels of the CCD detector. With an 8-bitCCD detector, each pixel value falls in the range of 0-255, with eachvalue in the range corresponding to a different shade of gray.

A CCD is a charge coupled device whose semiconductors are connected sothat the output of one is the input to another. A CCD camera is based onelectronic chips called CCD sensors. These components are sensitive tolight and allow pictures to be digitized and stored in computers. A CCDchip is an array of light-sensitive capacitors. The capacitors arecharged by the electrons generated by the light. Each light element thatreaches the CCD array displaces some electrons that are providing acurrent source. The current sources are localized in small delimitedareas called pixels. The pixels form a CCD matrix.

In particular, the surface layer of this chip contains a grid, and eachcell of the grid is a silicon diode which builds an electrical chargeproportional to intensity and time light falls on it. A dischargingcircuit is connected to all cells. Behind these cells is a matching gridof pixels (i.e., a CCD matrix). Each cell stores an analog voltagerather than an off-on (binary) value. The storage capacity of a pixel isalso referred to as a well, and the electric charge storage capacity ofa typical pixel can be several hundred thousand electrons.

Generally, the charges are converted to voltages through an analog todigital (A/D) converter. In the A/D converter, the electric charge of apixel is converted to an 8-bit number ranging from 0-255. The 8-bitnumber is referred to as a pixel data number. The pixel data numberrepresents the converted amplitude of each pixel. The noninvasivemeasurement system uses a black & white CCD television (TV) camera and apersonal computer. A fully portable version of the noninvasivemeasurement system that fits in the palm of one's hand is presentlypossible. A CCD camera uses 8 digits to represent the amount of lightenergy that hits the CCD surface. Because 8 digits are used to representthe amount of light energy, it can express brightness in 256 (0-255)levels.

In an alternative embodiment, a filter is used. In particular, a bandpass filter is placed in front of the camera lens and behind the light.This filters light to eliminate most of the visible spectrum. In yetanother alternative embodiment in which a filter is used, the lightwaves are cut off just before or after a particular wavelength value.

In an alternative embodiment, a digital camera is used. With a digitalcamera. 312 bits are used to represent the amount of light energy thathits the CCD surface. The 312 bits are used to represent the amount oflight energy ranges from 0 to 4096 (rather than 0 to 255). This leads tobetter resolution of the light energy.

C.2 Find Center of Pupil

The next processing step is to find the center of the pupil. Thenoninvasive measurement system centers the pupil on the image. Inparticular, while taking the picture, the image of the picture istransmitted by the camera to a computer having a monitor. Prior to“snapping” a picture for use in calculating a blood glucose value (i.e.,concentration), the noninvasive measurement system enables the eye to beadjusted relative to the camera lens to physically place the eyeball inthe center of the picture. Additionally, once the picture is taken, thepixels of the CCD matrix are stored in an array, sequentially, by roworder. The center of the array identifies the center pixel of thepicture. That is, the noninvasive measurement system finds the energycenter.

Having found the center of the pupil, the noninvasive measurement systemalso performs the following processes: zeroes-out the area within thelight source, to eliminate the light source from the pupil image,determines the eye registration within the camera frame and calculatesthe useful image area, grows a pupil mask from the light sourcecenterpoint and use it to cover the pupil area in the image, andcaptures the area under the aligned pupil mask for the dark-levelcalibration. These are discussed in more detail below.

C.3 Calculate the Average Brightness Around the Pupil Center

Next, the noninvasive measurement system calculates the averagebrightness around the pupil center. The noninvasive measurement systemtreats the pupil as a black dot. After finding the center of the pupil,the noninvasive measurement system takes 150 pixels horizontally andvertically from the center of the pupil and calculates an averagebrightness (i.e., this is the sum of the values of the pixels divided bythe number of pixels summed). This average is the average brightness ofthe center of the pupil. This will be used as a baseline value forfurther calculations.

C.4 Mask Pupil Region

The noninvasive measurement system masks out the pupil region of theeye. The noninvasive measurement system masks a central area, sufficientto cover a pupil. Different people have different size pupils. The areato be masked was a “sufficiently large” amount that would cover thepupil of most individuals. For one embodiment, this “sufficiently large”value was experimentally found to be about 90,000 square pixels. Thenoninvasive measurement system forms a sufficiently large box around thepupil and sets the pixels in this box to zero. The pupil is then a darklevel reference. The masking process results in excluding the pupil fromfurther processing. Thus, the noninvasive measurement system defines anumber of pixels in an iris that are to be processed.

Although different individuals have different sized pupils, by keepingthe mask the same size across individuals, the noninvasive measurementsystem processes approximately the same number of pixels for an irisacross different individuals. If changes in pupil diameter betweenindividuals and pupil centering are not held constant, the total numberof iris pixels available for integration will change. To control theseeffects, a software pupil mask is employed. This zeroes-out a fixedregion around the pupil.

The software pupil mask is larger than the largest pupil diameter andcovers pupil-centering errors. Some iris pixels may be zeroed in theprocess, but all image frames are treated in the same way. The pupilmask is preferably always the same size, and therefore all image framescontain the same number of iris pixels. The geometric distortions due topupil variations are eliminated.

In an alternative embodiment, the mask size may be determined based onan individual's own pupil size.

C.5 Equalize the Iris Image Using the Pupil Brightness as a LevelBaseline

The noninvasive measurement system also applies image contrastequalization, also referred to as stretch. This causes pixels to fillthe complete dynamic range of pixel data. The pupil baseline data isapplied to this process, permitting only the pixels that are brighterthan the pupil to be remapped. As a result, further processing takesplace using data that have been scene-level-biased and equalized to afull amplitude range.

Stretch takes an 8-bit number (i.e., the pixel data number) representingpixel data and remaps the pixel data number to the full dynamic range of0-255. The pupil, which has-been masked, contains all zeroes. So, forexample, if the brightest pixel is 95, the noninvasive measurementsystem may map the values 0-95 to 0-255, with 0-5 mapping to zero and90-95 mapping to 255. Thus, several values (e.g., 12, 13, and 14) can bemapped to the same number (e.g., 56). This resolves small variations inthe scene in the eye (e.g., tearing).

A technique called auto-stretch is used, which is well-known in theimage processing area. This compensates for small changes inillumination (e.g., the light source is drifting or if room light getsin as well as light transmitted by the noninvasive measurement system).This also deals with the problem in which light does not fall on an eyethe same for sequential pictures. Consistency is needed for betteraccuracy of the results. By weeding out variables, such as changes inlight, the noninvasive measurement system can detect that the changes inpixels represents a change in the level of glucose in the blood, ratherthan other changes.

Additionally, the noninvasive measurement system may use a gammastretch, which is a non-linear stretch. The gamma stretch takes care ofthe effects of bright sunlight. In particular, a gamma stretch amplifiesmore when there is darkness, and less when there is bright light. Mostcameras have gamma circuits. For the noninvasive measurement system, thehardware gamma stretch was turned off. However, in one embodiment, acontrolled software gamma stretch is used to enhance specific regions ofthe return levels (e.g., the bottom or top level of the picture).

C.6 Remove Hot Spots If Present

Hot spots are extraneous illuminations of light (e.g., outside light) oruneven illumination of the eye (e.g., light source is not over thecenter of the eye or there is a reflection of the light). Onceillumination set up, with the noninvasive measurement system, theillumination does not change. Therefore, the location of hot spots havebeen found by experimentation with light (e.g., can see light sourcereflected in the eye). This leads to customized masking based on aparticular illumination system.

To remove known hot spots, the noninvasive measurement system draws abox around the hot spot and zeroes the pixels in the box. The size ofthe box was experimentally found and differs based on the illuminationsystem used.

That is, good light source diffusion is needed to prevent hot spots.Additionally, the noninvasive measurement system performs hot-spotremoval with software masks. Thus peak signal amplitudes are removedbefore the integration process.

The noninvasive measurement system finds the light (seen as a hot spotin the center of the pupil) and performs a position alignment based onits location.

C.7 Integrate All of the Processed Iris Pixels

The noninvasive measurement system adds up the pixels that form thepicture of the eye. Because the pupil has been masked (i.e., set tozeroes), the pixels that are added are those of the iris. The sum of thepixels is referred to as an “integrated data number” or IDN. The IDNvalue is interchangeably designated “GLU”, for glucose value.

C.8 Search a Lookup Table to Find the Closest IDN-to-GL Match

The sum of the pixels provides an integrated data number (IDN). Thenoninvasive measurement system maps the IDN to a glucose level (GL)using an IDN-to-GL lookup table. It will be appreciated that the look uptable effectively provides a correlate of glucose concentrations. Thatis, it provides ranges of values that are correlated to differentglucose concentrations.

The process of converting the IDN to a true glucose measurement requiresa simple lookup operation to verify that the result is within apredetermined error band. The correlation from IDN to milligrams perdeciliter (mg/dl) can be seen in the following formula An programentitled “Average” (discussed in Section C.12 below) determines aminimum and maximum IDN value by comparing IDN values for a series ofimages of the same eye, taken in succession. Similarly, the programdetermines the minimum and maximum GL values by comparing GL values forthe same series of images. The program also determines the actualglucose level using the lookup table.

${IGN} = {{\frac{{IDN}_{\max} - {IDN}_{\min}}{{GL}_{\max} - {GL}_{\min}} \cdot {GL}} + {{IDN}_{\min}.}}$

These terms are defined as follows.

IGN=implied glucose number

IDN_(max)=highest possible IDN (integrated data number)

IDN_(min)=lowest possible IDN

GL_(max)=highest possible glucose value (in mg/dl)

GL_(min)=lowest possible glucose value (mg/dl)

GL=actual glucose value (mg/dl)

Inserting a milligram/deciliter value in GL yields its equivalent IDNvalue in IGN.

Going from IDN to GL is accomplished by searching or hashing a lookuptable. When the IDN value is equal or almost equal to a bounded IDNtable value, GL is retrieved from the table and output as the glucosereading.

The IDN lookup table is produced by averaging multiple calibrated IDNsamples for known glucose values. A fixed error range is based on aplus-or-minus deviation percentage from the average IDN. This ispreferably done for all available glucose numbers. Because it isdifficult to obtain values for every glucose number, values betweenknown samples can be interpolated to create a complete table. In oneembodiment, a limited range of measurements were used to produce a smallexample conversion table, which is shown above. One skilled in the artwould recognize that a larger database of images and experimental datamay be used to create an IDN-to-GL look-up table for a broader range ofglucose measurements.

The IDN-to-GL lookup table has columns for a minimum and maximum rangeof the IDN number. Each minimum to maximum range maps to a GL number.The IDN-to-GL table was calibrated by experimenting on an individual,Walter K. Proniewicz. Each experiment consisted of using a camera toobtain an image of an eye of the individual, calculating an IDN value,and obtaining a GL value for the individual using the noninvasivemeasurement system. Traditional (one-touch) glucose monitors were usedto verify the validity of the glucose concentration found via thetechnique of this invention. The IDN-to-GL lookup table was built byidentifying, by this experimentation a GL value that correlated toranges of the DN value.

The following is the IDN-to-GL lookup table that was calibrated for thenoninvasive measurement system:

MIN IDN MAX IDN GL 23092848 23155106 38 23221033 23310529 45 2590900925999999 84 23350883 23540368 109 23500534 23851841 175 2397830024034595 194 24047870 24052409 244

Experiments were performed on more than 20 other people. For theexperiment, each person was tested with the noninvasive measurementsystem and, for verification, tested with a traditional (one-touch)glucose monitor that samples blood. Each person then increased theirblood glucose levels (e.g., by eating donuts). Then, each was againtested with the noninvasive measurement system and, for verification,tested with a traditional (one-touch) glucose monitor that samplesblood.

The twenty people included were all adult subjects with one additionalknown diabetic. Their 18 men and 2 women. All subjects were caucasian. Alarge variation in pupil sizes was noted. Eye color was not recorded.Additional system sensitivity and accuracy can be obtained by capturingmultiple frames and summing their IDNs together. Changes due to smallmovements of the eye are thereby averaged out. Digitally summed IDN alsoincrease effective integration time, resulting in a larger dynamicrange.

C.9 Display the Imputed Glucose Number in GL

The noninvasive measurement system displays the GL value on a displaydevice connected to the computer, such as a computer monitor. Thecombined result of the camera/computer arrangement is a numeric outputthat displays blood-glucose levels in units of milligrams/deciliter, ona computer screen or small LCD display.

C.10 Details of Apparatus

A high-resolution black-and-white digital video camera assembly (FIG. 3)uses a charge-coupled detector (CCD) array as a sensor. The cameraincludes a body 310 for housing the CCD array, a mounting section 311with an attachment thread 329, a camera sync connector 312, and avideo-out connector 313.

It will be understood that all of the details presented here relate toexperimental prototypes that have been built and tested. Representativedimensions for the assembly follow.

REFERENCE NUMBER VALUE IN DRAWINGS (INCHES) 321 2.18 322 3.75 323 0.75324 0.69 325 0.75 326 2.38 327 1.25 328 1.40 An extension tube 314 holdsa 1:1.4 lens 315, making the focal length approximately 2½ cm (oneinch). The purpose of the extension tube is to maximize the amount ofdata from the iris 432 (FIG. 4) of the eye 430 and limit, to zero, theamount of white of the eye.

At the beginning of testing “Snappy™” shots were selected. A Snappydevise, manufactured by Play Inc., is an image-capture card for apersonal computer (PC). It captures a one-thirtieth-second frame from amoving image and stores it for future analysis.

Approximately forty percent of all frames were lost because of movementof the eye, reflections, and exposed white of the eye. The frames usedare advantageously similar; the total digital numbers are preferably asclose to each other as possible.

To produce optical data for the camera, a small light source 433 (FIG.2) directs light 434 toward the center of an eye 430, and reflections435 from the pupil 431 and iris 432 traverse the lens 315 to the CCDcamera 310. Note that no optical dispersing or wavelength-selectingdevice is included.

Thus the CCD camera 310 sees the reflected light 435 from the eye. Rawvideo data 437 go to a digital interface 438, which responds withcorresponding digital data 439 that proceed into a computer 440. Thecomputer may be a portable, self-contained unit that comprises a dataprocessing system (e.g., computer 440 or a microprocessor) and a wavereflection capture system or a receiver that receives wave data (e.g.,camera 310).

The central-illumination arrangement of FIGS. 3 and 4 was the successorto numerous earlier efforts based instead on diffuse illumination of anddata collection from the eye. In the first successful, repeatable one ofthose (FIG. 5), light from a forty-watt incandescent party bulb 543 wasintegrated by flat white paint on the walls of the roomitself—essentially a large integrating-sphere concept.

The light was arranged to approach the eye 430 at a right angle to theoptical axis 541 between the lens and the eye, to minimize formation ofreflections and shadows. To minimize the problem of hot spots andresulting high data counts, mostly caused by bare exposed lightbulbs,the illumination was passed through a diffuser 542—created from a plainwhite paper cylinder placed around the light source.

To lessen the difficulties of repeating frames and holding the CCDcamera steady, and to shield and eliminate reflections, an optical benchwith a foam ocular 645 (FIG. 6) was built. In addition, a headrest (FIG.7) helps stabilize the eye.

The optical bench, three feet long, was fashioned from two aluminumrails 647 (FIG. 6)—a rectangular one, lying horizontal, and a square barturned on the diagonal so that one corner fits into correspondingnotched grooves in the base 648 of the headrest and in the base of thecamera support. The bar allows movement only along the z-axis (i. e.,longitudinally). This geometry also allows setting of distances betweenthe headrest (i. e., the eye position) and the camera.

The support stand allows up-and-down (y-axis) adjustment by means of avertical rod with an adjustment knob. The two rails are kept parallel bybeing mounted on two eight-inch crossbars with three legs made frommachinist jackscrews. One leg is attached to the center of thecross-bar, the other two legs are attached at opposite ends of the othercrossbar, thereby allowing leveling in a classical manner.

The headrest is mounted to a sliding aluminum base 648, to support twoone-foot-long threaded vertical rods 754 holding a curved aluminumforehead piece 646. The whole mechanism is mounted on a centeredvertical support rod 753. A crossbar 752 supports a subject's chin on asoft pad (not shown), and the forehead rests against the forehead piece646 to stabilize the head. Adjustment and locking are facilitated by anadjustment screw 752.

The CCD camera is also mounted on a support rod, set in a commercialsupport stand. The rod is attached to the camera, which is inside atubular cardboard light shield 649 (made from a cardboard mailing tube).A trapdoor allows for adjustments to the camera with two camera-supportscrews through the tubular shield, centering the camera in the shield.

The tube is four inches in diameter and fourteen inches long. Thetrapdoor is eight inches long and sections out half of the tube,starting one inch back from the front. The camera lens face is flushwith the end of the tube. The interior of the tube is painted flatwhite.

Various other experimental setups included some geometries with twotubes—one for each eye, with an eye-tracker disc placed in front of theeye not being sampled. In one embodiment, a system with no ocular lensand in which the nondata eye is exposed is used.

In one experimental setup, a pair of slip-tube swing arms 869 (FIG. 8)fixed to the camera mounts—above and below the tubular shield 649—held avertical rod 861 on which a block 862 slides up and down 864, carrying alight-emitting diode (LED) 863. The LED served as the light source forcentral illumination. The slip tubes enabled horizontal adjustments 866,and the LED block vertical movement 864.

The next development in experimental progression eliminated use of amechanical eye-tracker. A video monitor is used to show real-time videoof the eye being viewed for data collection.

The subject views his or her own eye on the monitor, and can rapidlycorrect for positioning of the eye, thus minimizing the amount of whiteof the eye showing—and allowing for detection of unwanted reflections.Looking at a real-time video is faster and easier than doingeye-tracking using the mechanical tracking system.

Selected single frames were stored using a frame grabber or Snappy™image-capture card. In this process, data collection took a long timebecause flames with high data error—usually half of the frames taken—hadto be discarded.

Next a video recorder was employed. For experimental purposes the starttime, lamp color, filters, blood glucose values, commentary and end timewere annotated audibly.

Four to five minutes of video data were taken continuously. The endresult was thousands of frames (at a frame rate of thirty per second)from which to handpick later.

Good frames could be selected, saving a great amount of time. This isalso proved that the accuracy and repeatability were very high, muchbetter than current blood-glucose meters on the market.

Experimental work also explored numerous illumination arrangements withmultiple light sources, including arrayed LEDs of different colors invarious geometries. Currently favored illumination geometry, however, asnoted earlier provides a single light source such as an LED 433 (FIG.10).

In the best of these configurations, the LED was held centered by adiametral vane or web 972 (FIGS. 9 and 10) with a hollow central hub 973for the LED, in an aluminum bezel 971. The LED is held in front of thecamera lens and aimed at the eye.

The back of the LED is covered with black tape 1081 to shield the lens(surface) 315 so that none of the direct LED light is picked up by thecamera. Only the light reflected by the pupil 431 and iris 432 is seenby the camera. This scheme also enables the subject to center thesubject's own eye by looking directly into the LED—or a grain-of-wheatsize incandescent bulb.

Bezels were made to accommodate two sizes of LED: a so-called “T1” 3 mmand a “T-1¾” (5 mm). The larger LED masks the entire pupil—therebynegating the data that would be gathered for pupil calibration. The datacollected is nevertheless very useful in obtaining the correction factorto establish total system linearity.

The bezel portion that goes over the lens shade has a 1.39 inch insidediameter, with a 0.05 inch wall, 0.3 inch deep. The web that holds theLED has a thickness of 0.04 inch (to minimize the masking of data fromthe iris to the CCD camera) and is 0.125 inch deep.

A goal during data-taking is to illuminate the iris to the point, atleast, ½ full well on the total digital number (D/N) possible—oralternatively full well of the CCD camera. Empirical data-collectionand—manipulation suggests that ¼ full well may be a minimum needed toprovide the amount of data necessary for all manipulation ofcalibration, subtraction and averaging for an experimental system.

Although the embodiments described above have employed a personalcomputer (PC) for data manipulation to get a glucose value, theinvention contemplates, as a first step toward portability, making ahybrid integrated circuit to replace the PC. It also appears worthwhileto develop a “foolproof” transmitter coded to transmit blood-glucosevalues directly to a diabetic's insulin pump, as well as calculation ofutilization time and amount of insulin. Eventually continuous readingsthrough a convenient means, such as for example eyeglass-mountedsensors, would bring the diabetic and others back to a more-normal life.

C.11 Wavelength Effects

The glucose response has been observed over portions of the visible andnear infrared portions of the light spectrum. Peak response appears tobe in the yellow and yellow/green and near infrared portion of thespectrum for the algorithm described above.

It is reasonable to generalize the foregoing observations to note whatis common to both wavelength regions—i.e. that the level response issubstantially monotonic, namely either an increasing function or adecreasing function for the different wavelength regions respectively.

In one embodiment, a black-and-white CCD array is able to collectsufficient information for blood-glucose determination—reflected lightlevel being distinctly correlated with glucose concentration.

This is accomplished through heavy reliance upon further softwaremanipulation of the data. Such operation is mechanically and opticallysimpler than, and is to be distinguished from, the measurement mode thatis was embodied in earlier prototypes of the apparatus, which employedrotating filter wheels to perform rudimentary spectral differentiation.See referenced United States Provisional Patent Application 60/100,804,“BLOOD SUGAR MEASUREMENT THROUGH THE EYEBALL”, filed on Sep. 18, 1998,by Walter K. Proniewicz and Dale E. Winther, which is incorporated byreference herein.

C.12 Image-processing Software

Two programs, “Glucon™” and “Average”, were written for implementationof the present invention and were instrumental in performing researchand obtaining quantitative results from experimentation. Both programswere developed using a graphical programming language from NationalInstruments Corporation known as “G™”, and also known as LabView™5.0—with the IMAQ™ imaging tools. The description above, including thepseudo-code describes the processing of these programs.

The first program, Glucon, extracts information from light wages. Itembodies all necessary techniques for obtaining IDN or GLU values. Thesecond program, Average, is used to correlate the IDN or GLU valuesobtained from an imaged eve with the actual concentration of patientblood glucose. It processes a user-selectable number of images of asubject eye, all taken at a particular glucose level, i.e. in quicksuccession. In operation, Average creates a statistical box and thenobtains the average and absolute IDN or GLU limits. These values areused to build a table of IDN-to-blood-glucose conversions.

FIG. 11 illustrates a control panel 1100. While the noninvasivemeasurement system is imaging a subject eye with the camera, thenoninvasive measurement system displays a control panel on the computerscreen that includes various buttons and other controls along with twoimages (Image A 1102 and Image B 1104). Image A and Image B are twoseparate images of the same eye, taken at different times, that may bedisplayed together for comparison. However, the noninvasive measurementsystem can also display just one of the images. Image A and Image B aredisplayed by the noninvasive measuring system as false color intensitymaps. These images, however, are in black and white format in theattached figures. The center of an image is the pupil and is masked(i.e., zeroed out, which corresponds to a black color). Around thepupil, the dark color is actually red and indicates that theconcentration of blood glucose in the eye is high. The GLU or IDN valuesin milligrams per deciliter (mg/dl) are calculated from the images.Image A and Image B are provided for ease of understanding of theinvention, but they are not required to practice the invention.

The control panel 1100 includes an X control that enables setting afilter factor. The Filter control turns a filter on or off. The Mean Acontrol provides the mean of Image A. The DEV A control displays thestandard deviation for Image A. The Mean B control displays the mean ofImage B. The DEV B control displays the standard deviation of Image B.The GRU A control displays the GRU value for Image A, and the GRU Bcontrol displays the GRU value for Image B. The BLK A&B controls displaythe number of dark pixels (0DN) in the A&B images, respectively. The LOcontrol sets a minimum stretch limit. The HI control sets a maximumstretch limit. The THRESH control sets a threshold, so that when the IDNis being summed up, if the threshold is set, the summing begins at thatlevel but does not include any pixels below that level. The GLIM controlindicates that the IDN summation will not include values above this. TheBIAS A control adds to the average level of brightness of the pupil forImage A. The BIAS B control adds to the average level of brightness ofthe pupil for image B. The LEVEL A&B controls indicate the averagebrightness of the pupil for each image. The PATH A and FILENAME Aprovide the path and filename used to locate the storage location ofImage A. The PATH B and FILENAME B provide the path and filename used tolocate the storage location of Image B. The GAMA control is a gammastretch control. The F MODE control select the different filter shapemodes.

The XPOS control provides a readout of the X position of the mouse on animage, and the YPOS control provides a readout of the Y position of thecursor on an image. Together, the XPOS and YPOS enable selection of aparticular pixel. The DN control displays the data number of the pixellocated under the cursor. The DELTA control shows the difference betweenthe line or row image segment sums between the A and B frame. These arethe cumulative values of the pixels shown in the 2 waveform charts shownin FIG. 11. The Switch marked SUM X/SUM Y selects between row andcolumns in the image and these data are summed. The sums are comparedand displayed by the DELTA control. The CENT A&B controls indicate the Xand Y position of the centroid of the respective image. The A&B LINEScontrol permits user manipulation of the SUM charts in FIG. 11. TheSUGAR A control displays the glucose level that correlates to Image A.The ERROR A control is lit when an error is detected. When the ERROR Acontrol is lit, the SUGAR display is blanked out. The NEG control is redwhen the second frame (i.e., image B) has a smaller GRU that of thefirst frame (i.e., Image A). It is green when the second frame has alarger GRU than that of the first frame. The STR control turns on aprimary linear stretch. The COL control allows selecting false color orblack and white, the SUM X and SUM Y control enables showing the sum ofX or the sum of Y in the graphs for the two images. The A+B controlindicates that two channels (i.e., two images) are being processed. TheBW control enables setting the background of the graph to be black orwhite. The CLONE control enables cloning the second frame into the firstframe. Then, if desired, a new frame can be brought into the secondframe, to continue comparisons between different frames. The 3D controlindicates whether the images are to be show as pseudo 3D. The PCUTcontrol sets the pupil cutter to on or off. The ICUT control sets theIRIS cutter (leaving only the pupil) to on or off. The CAL control isset to on for calibration of the pupil for a linear stretch. The STOPcontrol stops the program. At this time, the picture may be manipulated(e.g., moved horizontally or vertically and the mouse can be used tomove the cursor about to identify individual pixel values). The SNAPcontrol invokes a program to snap a picture of the screen and store itas a bitmap. The SAVE button directly saves the picture as a bitmap. TheSUGAR B control displays the glucose level that correlates to Image B.The Error B control is lit when an error is detected.

FIG. 12 are representative histograms that are another part of the samecontrol panel display, particularly showing histograms representingresults of different processing stages within the program. Histogram A11200 represents Image A (from FIG. 11) initially. Histogram A2 1202represents Image A after data was normalized and stretched. Similarly,Histogram B1 1204 represents Image B (from FIG. 11) initially. HistogramB2 represents Image B after data was normalized and stretched

FIG. 13 is a display of a control panel associated with an averageprogram and having controls used to correlate typical values with anactual concentration of patient blood glucose in conventional units. TheAverage program is used by the noninvasive measurement system to obtaincalibrated IDN-to-GL data from the IDN values. The COUNT control selectsthe number of image frames to be processed in the calibration average.The AVNUM control is the average GRU obtained from the selected frames.The AVPIX control is the average pixel brightness for all of the inputimages in the GRU average. The PATH and FILENAME controls display thepath and file name of the last image being processed. The AVMIN controlis the minimum average GRU from all of the processed images. The AVMAXcontrol is the maximum average GRU from all of the processed images. The+DELTA control indicates the GRU error delta from the average GRU in thepositive direction. The −DELTA control indicates the GRU error deltafrom the average GRU in the negative direction. The +PRCNT controlindicates the maximum GRU error percentage above the average. The −PRCNTcontrol indicates the minimum GRU error percentage below the average.The CAL control enables the pupil calibration to be applied to theAutomatic Stretch algorithm. The PCUT control sets the pupil cutter toon or off. The GLIM control indicates that the IDN summation will notinclude values above this. The LEVEL control indicates the average pupilbrightness.

C.13 Glaucoma Measurements

The noninvasive measurement system also uses the curvature of the iristo obtain glaucoma pressure at close focal length. An eve machine can beused to automatically give a difference in comparative focal lengths ofinner iris vs. outer iris as an indicator of pressure.

FIG. 14 illustrates the use of the noninvasive measurement system toidentify glaucoma pressure. The distance F_(iris ID) represents thedistance from the vertex plane of a CCD camera lens 315 to the insidediameter (ID) of the iris—in other words, to the circular transitionbetween the iris 432 and the pupil 431. Analogously F_(iris OD)represents the distance from the lens vertex plane to the outsidediameter (OD) of the iris—i. e., to the circular transition between theiris 432 and the white 1400 of the eye 430.

In the upper “A” view, these two distances F_(iris ID) and F_(iris OD)are substantially equal, F_(iris ID)=F_(iris OD). This indicates abalanced or normal pressure condition within the eye. In the lower “B”view, the two distances are no longer equal: specifically, the IDdistance now exceeds the OD distance, F_(iris ID)>F_(iris OD), therebyindicating abnormal, excessive pressure.

The incremental distance 1402, which is to say the differenceF_(iris ID)−F_(iris OD) (or ratio) between the two distances, is relatedto pressure. Focal determinations thus yield a measure of intraocularpressure, a large distance corresponding to high pressure and a smalldistance to low pressure. Depth of field, for example 0.3 mm (0.012inch), may form a limitation on this technique.

C.14 Flow Diagram and Alterative Embodiments

The noninvasive measurement system comprises apparatus and software fornoninvasively measuring glucose concentration in blood. To reduce thecomplexity of the image-input system, software has been developed tooptimize camera positioning and illumination consistencies.

FIG. 15 is a flow diagram illustrating the steps performed by thenoninvasive measurement system in one embodiment of the invention. Inblock 1500, the noninvasive measurement system images the eyeball. Inblock 1502, the noninvasive measurement system finds the center of thepupil. In block 1504, the noninvasive measurement system calculates theaverage brightness around the pupil. In block 1506, the noninvasivemeasurement system masks out The pupil region of the eye. In block 1508the noninvasive measurement system equalizes the iris image using thepupil brightness as a level baseline. In block 1510, the noninvasivemeasurement system removes hot spots, if any are present. In block 1512,the noninvasive measurement system integrates all of the processed irispixels. In block 1514, the noninvasive measurement system searches aIDN-to-GL lookup table to find the closest IDN-to-GL match. In block1516, the noninvasive measurement system displays the imputed glucosenumber.

The noninvasive measurement system has several facets or aspects whichare usable independently, although for greatest enjoyment of theirbenefits they are preferably used together and although some of them dohave some elements in common.

In embodiments of a first of its independent aspects, the noninvasivemeasurement system measures blood-glucose concentration in a biologicalentity by measuring light reflectivity from the body. The noninvasivemeasurement system includes a technique for directing light to such body(e.g., a light bulb). In addition the noninvasive measurement systemincludes a technique for receiving (e.g., with a camera) and processing(e.g., with a computer) light reflected from such body substantiallywithout spectral analysis of the reflected light. The foregoing mayrepresent a description or definition of the first aspect or facet ofthe invention in its broadest or most general form. Even as couched inthese broad terms, however, it can be seen that this facet of theinvention importantly advances the art.

In particular, this facet of the invention entirely eliminates need forpiercing the body or otherwise obtaining blood samples, and so avoidsthe discomfort, fear and other detriments discussed above. Furthermorethis aspect of the invention is advantageous in that it requires noelaborate spectral modulation, or multiple detectors for differentwavelength regions, or dispersive elements—such as required to performspectral analysis.

The absence of requirement for spectral analysis is a direct result ofthe discovery that light reflected from the iris bears a monotonicrelationship (though different in different wavelength regions) toglucose concentration in the blood.

Although the first major aspect of the invention thus significantlyadvances the art, nevertheless to optimize enjoyment of its benefitspreferably the invention is practiced in conjunction with certainadditional features or characteristics. In particular, preferably thetechnique for directing light to an eve of the body and the techniquefor receiving and measuring include a technique for receiving andmeasuring light reflected from the eye.

Further preferably the receiving and measuring a technique comprises amonochrome detector array—and in this case still more preferably themonochrome detector array comprises a black-and-whitecharge-coupled-detector (CCD) camera or detector. Another relatedpreference is that the receiving and measuring a technique includes adigital processor for analyzing signals from the CCD camera.

More generally, such a processor is desirable for analyzing signalsrepresentative of quantities of the reflected light. In this case onepreference is that the digital processor be part of a personal computer,and the blood glucose level is reported on a monitor screen of thecomputer.

An alternative preference, however, is that the noninvasive measurementsystem be a handheld portable unit, that the unit include a techniquefor reporting for indicating the blood glucose level, and that thedigital processor be part of the handheld portable unit. In this casepreferably the reporting technique includes an LCD unit for visuallyindicating the blood glucose level.

Another basic preference is that the receiving and measuring techniqueincludes a technique for detecting change in level of the reflectedlight, and relating said change to blood-glucose concentration. Stillanother is that the receiving and measuring technique include sometechnique for detecting change in level of the reflected light—and alsosome technique for reporting glucose concentration that variessubstantially monotonically with reflected-light level. Another generalpreference is that the detecting technique include some technique forresponding to reflected visible light and, in this case, particularly tolight in the yellow, yellow-green and infrared portions of the spectrum.

Although the noninvasive measurement system has been described asoperating substantially without spectral analysis, this is not intendedto imply that the noninvasive measurement system is necessarily entirelyunable to differentiate between spectral regions. For instance,preferably the noninvasive measurement system includes a technique foreliminating response to some particular light band—e.g. the red orinfrared, or both. Similarly the technique for receiving and measuringsubstantially without spectral analysis preferably do take into accountdifferent signal responses in the red or infrared as opposed to theyellow/yellow green portion of the spectrum.

In embodiments of a second major independent facet or aspect, thenoninvasive measurement system measures blood-glucose concentration in abiological entity by measuring light reflectivity from the body. Thenoninvasive measurement system includes a self-contained case. It alsoincludes a technique for directing light to the body. Also included is atechnique for receiving and measuring light that is reflected from thebody. The foregoing may represent a description or definition of thesecond aspect or facet of the invention in its broadest or most generalform. Even as couched in these broad terms, however, it can be seen thatthis facet of the invention importantly advances the art.

In particular, because it has been established through experimentationand testing that the entire invention is capable of reduction to becarried within a self-contained case, the many benefits of noninvasivemeasurement can be enjoyed in a unit that need not take the form of amachine only suited for use in a medical facility. Rather, the inventioncan be implemented in a machine suited for patients' use at home, or atan ordinary office or other business—or in cars, restaurants, etc.

Although the second major aspect of the invention provides significantadvantageous features, nevertheless to better optimize enjoyment of itsbenefits preferably the invention is practiced in conjunction withcertain additional features or characteristics, in particular,preferably the case is fully portable. Also in this instance preferablythe case fits in the palm of a normal-size adult's hand.

In embodiments of a third of its major independent facets or aspects,the noninvasive measurement system measures blood-glucose concentrationin a biological entity by measuring light reflectivity from an eye ofthe body. The noninvasive measurement system includes a technique fordirecting light to an iris of such eye. It also includes a technique forreceiving and measuring light reflected from such iris. Also included isa programmed digital processor that analyzes the measured reflectedradiation and computing blood glucose concentration therefrom—and inparticular uses a reflection of the light source, from the eye, as apeak amplitude point for image alignment. The foregoing may represent adescription or definition of the third aspect or facet of the inventionin its broadest or most general form. Even as couched in these broadterms, however, it can be seen that this facet of the invention providesimportantly advantageous features.

In particular, the eye is generally available for optoelectronicmeasurements without the subject's disrobing or any other greatinconvenience. Moreover, condition of the blood in the eye is generallyparticularly rapid in its response to or tracking of the condition ofthe blood in other critical parts of the body particularly the brain.

Although the third major aspect of the invention provides significantadvantageous features, nevertheless to better optimize enjoyment of itsbenefits preferably the invention is practiced in conjunction withcertain additional features or characteristics. In particular,preferably the receiving and measuring technique also includes atechnique for receiving and measuring light from a pupil of the eye.This preference facilitates determination of a baseline dark level, orof an illumination level provided by the light directing technique, orboth.

In embodiments of a fourth of its major independent facets or aspects,the noninvasive measurement system is a blood-glucose measuringtechnique. The technique includes the step of imaging forward surfacesof a person's eye on an electronic camera. It also includes digitizingresultant image signals from the camera. Further the technique includesprocessing pixel signals representing the iris, separately from pixelsignals representing other parts of the eye, to determine blood-glucoselevel. The foregoing may represent a description or definition of thefourth aspect or facet of the invention in its broadest or most generalform. Even as couched in these broad terms, however, it can be seen thatthis facet of the invention importantly advances the art.

In particular, analysis of conditions in the iris is advantageous inthat the iris exhibits monotonic relationships (peculiar to differentwavelength regions) between reflected light level and glucoseconcentration, enabling enjoyment of the previously mentioned benefitsof measurement without spectral analysis.

Furthermore the separation of iris and pupil signals for processing isamenable to straightforward implementation based upon geometry, leadingto easy compensation for varying illumination level and the like aspreviously mentioned.

Although the fourth major aspect of the invention thus significantlyadvances the art, nevertheless to optimize enjoyment of its benefitspreferably the invention is practiced in conjunction with certainadditional features or characteristics. In particular, preferably thetechnique also includes the steps of processing pixel signalsrepresenting the pupil to obtain a baseline dark level or anillumination level, or both—and also applying the dark level orillumination level, or both, to refine the pixel signals representingthe iris. In this case advantageously the processing step includesapplying an average reflected intensity level of the pupil to representthe dark level baseline.

Another general preference is that the iris-pixel signal processingcomprises integrating all usable iris-pixel signals to produce a unitaryintensity indication, in this case preferably the applying step includesintegrating into the indication only—intensities that are higher thanthat of the pupil.

Yet another basic preference is to include the step of substantiallyremoving image scene and illumination variation. Still anotherpreference is to include the step of calibrating readings for anindividual patient.

Another general preference is to include masking out the pupil pixelsfrom the iris region. In this case the masking step also preferablyincludes applying a software pupil mask that substantially stabilizesthe number of iris pixels available for use, and substantiallystabilizes pupil centering within the iris image. Further if this isdone preferably also the pupil mask is larger than the largest pupildiameter occurring in measurement conditions.

Other general preferences relative to the technique of the inventioninclude these steps, considered individually:

-   -   masking out the pupil pixels from the iris region;    -   diffusing source light to minimize hot spots;    -   removing peak signal amplitudes, to minimize the effect of        illumination hot spots;    -   mapping illumination hot spots, to enable disregarding 5        hot-spot regions in said processing step;    -   adjusting image contrast to substantially fill the complete        dynamic range of pixel data words;    -   looking up the measured level in a lookup table to obtain a        corresponding numerical blood-glucose concentration indication        in quantity of glucose per unit blood volume; and    -   said digitizing step comprises distinguishing very low        light-intensity changes.

Another preference, still as to the fourth aspect of the invention, isthis sequence of steps:

-   -   finding a center of the pupil of the eye; calculating average        brightness around a pupil center;    -   masking out the pupil region of the eye;    -   a equalizing the iris image using the pupil brightness as a        level baseline;    -   removing hot spots if present;    -   integrating all of the processed iris pixels to obtain a        numerical representation of brightness level of the iris;    -   searching a lookup table to apply a previously developed        calibration and thereby determine an imputed glucose        concentration in quantity of glucose per unit volume; and    -   displaying the imputed glucose concentration.

In embodiments of a fifth major independent facet or aspect, thenoninvasive measurement system is a blood-glucose measuring techniquefor use with a small light source. This technique includes the step ofautomatically finding a reflection, from a patient's pupil, of thelight. The technique also includes the step of automatically performinga position alignment based upon the location of the reflection of thelight. The foregoing may represent a description or definition of thefifth aspect or facet of the invention in its broadest or most generalform. Even as couched in these broad terms, however, it can be seen thatthis facet of the invention importantly advances the art.

In particular, this mode of operation very easily resolves severalotherwise knotty problems of alignment, which can otherwise threaten theintegrity of the overall measurement process—since the process issensitive to alignment and control of signal returns from the white ofthe eye as well as the pupil.

Although the fifth major aspect of the invention thus significantlyadvances the art, nevertheless to optimize enjoyment of its benefitspreferably the invention is practiced in conjunction with certainadditional features or characteristics. In particular, preferably thetechnique also includes zeroing-out the area within the light source, toform an image of forward surfaces of the eye without the light source.

Another preference, especially when the technique is for use with acentrally disposed light source, is the step of growing a pupilmask—starting from the light source as a centerpoint—to cover the pupilarea in the image. In this case, preferably the technique also includescapturing brightness level in an area under the aligned pupil mask, foruse in a dark-level calibration.

In embodiments of a sixth major independent facet or aspect, thenoninvasive measurement system measures blood glucose concentration in abiological entity by measuring light reflectivity from an eye of thebody. This noninvasive measurement system includes a detector array. Italso includes a small light source held-directly in front of thedetector array, for directing light to the eye. In addition thenoninvasive measurement system has a technique for receiving andmeasuring light reflected from the eye. The foregoing may represent adescription or definition of the sixth aspect or facet of the inventionin its broadest or most general form. Even as couched in these broadterms, however, it can be seen that this facet of the inventionimportantly advances the art. In particular, use of a source in thedescribed position greatly simplifies, in several ways, the processingof data derived from the optical system.

Although the sixth major aspect of the invention thus significantlyadvances the art, nevertheless to optimize enjoyment of its benefitspreferably the invention is practiced in conjunction with certainadditional features or characteristics. In particular, preferably thenoninvasive measurement system also includes a lens between the detectorarray and the light source.

In this case, it is that the light source shine toward the eye fromsubstantially the geometric center of the lens—or, alternatively of thedetector array. In this case the noninvasive measurement system furtherincludes a technique for using a reflection of theelectromagnetic-radiation source, from the eye, as a peak amplitudepoint for finding the image center.

A more general preference, still as to this sixth main aspect of theinvention—and especially when the noninvasive measurement system is foruse in measuring blood-glucose concentration for the body of a humanbeing—is that the light source serve as a visual centering target forthe human being. In such a system, the human being looks substantiallydirectly toward the light source to, in substance, automatically alignor center (at least approximately) the pupil in the optical field.

In embodiments of a seventh major independent facet or aspect, thenoninvasive measurement system measures blood glucose concentration in abiological entity, by measuring light reflectivity from blood of thebody. The noninvasive measurement system includes a technique fordirecting light to the blood. It also includes a technique for receivingand measuring light reflected from the blood substantially withoutspectral analysis of the reflected light.

From all the discussion, in this document, of aspects of the invention,those skilled in the art will understand that the invention operates, inone way or another, based upon presence of the blood in the iris orelsewhere within the body—thereby making the blood available foroptoelectronic measurement. Accordingly the invention is not limited tothe implementations expressly set forth.

D. Noninvasive Measurement of Glucose Concentration in an Eye Using aPhase Angle and Amplitude

Light is an electromagnetic wave. A wave has an amplitude, which is itspositive or negative displacement from an equilibrium point. A glucosemolecule rotates in a clock-wise direction as its density increases. (Onthe other hand, a fructose molecule rotates in a counter-clockwisedirection, and the noninvasive measurement system can distinguishbetween these molecules based on their rotation.) This clock-wiserotation affects the polarization. In one embodiment, the inventiontakes into account that rotation affects polarization. The more glucosethere is in the blood, the more light that is reflected. In particular,with polarization, there is a flash of reflected light (as reflectiveportion of glucose is struck by light), then no reflection (as glucoserotates such that the light strikes, for example, blood, which absorbsthe light), another flash of reflected light, etc. The light that isreflecting at different angles appears to be rotating, therefore, theamplitude changes.

A CCD is a charge coupled device whose semiconductors are connected sothat the output of one is the input to another. A CCD camera is based onelectronic chips called CCD sensors. These components are sensitive tolight and allow pictures to be stored in computers. A CCD chip is anarray of light-sensitive regions called wells. The wells are charged bythe electrons generated by the light. Each light element that reachesthe CCD array displaces some electrons that are providing a currentsource. The current sources are localized in small delimited areascalled pixels. The pixels form a CCD matrix.

In particular, the surface layer of this chip contains a grid, and eachcell of the grid is a silicon diode which builds an electrical chargeproportional to intensity and time light falls on it. A dischargingcircuit is connected to all cells. Behind these cells is a matching gridof pixels (i.e., a CCD matrix). Each cell stores an analog voltagerather than an off-on (binary) value. The storage capacity of a pixel isalso referred to as a well, and the electric charge storage capacity ofa typical pixel can hundreds-of-thousands of electrons.

The charges are converted to voltages that can be interpreted by ananalog to digital (A/D) converter. In the A/D converter, the electriccharge of a pixel is converted to an 8-bit number ranging from 0-255.The 8-bit number is referred to as a pixel data number. The pixel datanumber represents the converted amplitude of each pixel. In analternative embodiment, the pixel data number may be “stretched”. Thatis, if the pixel data number is 16, the numbers 0-16 may be mapped to0-255, so that the stretched pixel data number is 255 (i.e., 16 may bemapped to 255). Of course, one skilled in the art would recognize thatother mapping mechanisms may be used (e.g., mapping 0-31 to 0-255, with16 mapping to 127).

The image of the eye is used to form a CCD array, which is also referredto as a CCD matrix. The CCD matrix represents each pixel with an entryin the matrix. Each entry has a value ranging from 0-255. The phaseangle is determined from a CCD matrix. The rows of the CCD matrix aresummed up, and then these values are totaled to form an XGRU value. Thecolumns of the CCD matrix are summed up, and then these values aretotaled to form a YGRU value. The ratio of the XGRU value and the YGRUvalue results in the phase angle. For example, if the light fallssymmetrical, the XGRU value and the YGRU value are the same. However,for a substance, which is non-symmetrical, the XGRU value and the YGRUvalue are not the same. Additionally, the sum of the XGRU and the YGRUis the amplitude.

The following sample CCD matrix is provided only for illustration. Oneskilled in the art would recognize that a much larger matrix would inpractice be used. Also, to simplify the illustration, each pixel will beset to one of three states: 0, 1, 2. Of course a pixel can be of 0-255states for an 8-bit system, and a pixel can have greater resolution witha larger bit system. The following is a sample CCD matrix:

0 1 2 0 3 2 2 1 0 5 1 2 1 1 5 1 0 0 1 1 4 5 4 2

The noninvasive measurement system obtains row information YPA(summation of rows) and column information YPB (summation of columns)and calculates a true phase angle and a true GRU/true amplitude with thefollowing:

${{true}\mspace{14mu}{phase}\mspace{14mu}{angle}} = {\frac{{YPA} - ( {{YPA} - {YPB}} )}{{YPB} - ( {{YPB} - {YPA}} )} \times 10\mspace{14mu}{MILLION}}$true GRU/true amplitude GRU=(YPA+YPB).

For example, using the above matrix, the summation of the rows is(3+5+5+1)=14=YPA. The summation of the columns is (4+5+4+2)=15=YPB. Thetrue phase angle is equal to approximately 10714285. The true amplitudeis equal to GRU−(YPA+YPB), which calculates the amplitude by removingthe phase angle. Note that the true amplitude GRU is calculated bysumming all of the pixels when the matrix is at 680×480, while YPA andYPB are calculated for a reduced size matrix of, for example, 380×380.

The noninvasive measurement system uses a Phase/Amplitude lookup table.The Phase/Amplitude lookup table has columns for a frame cousin number(FRC), a glucose level (GL), an amplitude (AMPL), and a phase angle(PHASE). The Phase/Amplitude lookup table was created experimentally. Inparticular, the Phase/Amplitude table was created by experimenting on anindividual, Walter K. Proniewicz. Each experiment consisted of using acamera to obtain an image of an eye of the individual, calculating a GLvalue for the individual, and calculating a phase angle and amplitude.Traditional (one-touch) glucose monitors were used to verify thevalidity of the glucose concentration found via the technique of thisinvention. The Phase/Amplitude lookup table was built by identifying, bythis experimentation. GL values that correlated to a phase angle andamplitude pair.

Additionally, the noninvasive measurement system uses a Cousins table.The cousins table has a column for a FRC number (frame cousin), aglucose level (MG/DL), an amplitude (AMPL), a phase angle (PHASE), andcolumns for eight cousins. One skilled in the art would recognize thatthe table could have other columns, for example, additional columns formore than eight cousins. The cousins represent nodes that have similarphase angle and amplitude values. The NODE TABLE DATA graph is a graphof phase angle versus amplitude. The top most line in the graph plotsthe ratio of phase angle to amplitude. The cousin nodes in the Cousintable are nodes that are at approximately the same horizontal axis onthe plot of the ratio. For example, for FRC 10, the cousins are FRC 25,FRC 28, FRC 23, FRC 29, and FRC 18. Each of these frame cousins has asimilar phase angle to amplitude ratio.

D.1 Overview of Processing

One embodiment of the invention uses the phase angle and amplitude toidentify a blood glucose level. This section provides an overview of theprocessing steps for this embodiment of the invention, along withpseudo-code. Only some of the processing steps will be discussed here toenable the reader to have a better understanding of these steps prior toproviding the pseudo-code. Generally, when a Phase/Amplitude LookupTable is used, the noninvasive measurement system performs the followingsteps:

1. image the eyeball, with center brightness

2. apply a spatial filter

3. perform automatic level control

4. find a true GRU

5. automatic fine tuning

6. display the identified glucose number

The picture may be taken with a black and white video or electronicstill frame camera. In an alternative embodiment, a color camera orcustom CCD may be used. In yet other embodiments, other detectors, suchas quantum well infrared arrays or mercad telluride arrays orspecialized radio receivers can be used.

In one embodiment, a calibration mask is used. The calibration mask isplaced between the eye and the lens of the camera. For example, onecalibration mask may be a circular piece of glass. Imagine a squarewhose corners touch the circle is drawn on the circle, then, reflectivestrips of the material to be analyzed (e.g., glucose) are placed betweenthe edge of the square and the edge of the circle, in vertical lines,with one endpoint of the strip touching the square and the otherendpoint of the strip touching the circle. The material to be analyzedmay be placed on a mask and then sealed. The mask is placed so that thelens system and CCD can see the mask and so that the mask is illuminatedby the light source.

The reflective strips have known phase angle and amplitude values. Eachstrip has different phase angle and amplitude value. For example, eachmay represent 5 mg/dl increments starting with 35 mg/d. A strip may bethe size, for example, of 50 pixels. The number of strips used is thesize of the strip divided by the number of pixels to be covered. Thecomparison will assist in increasing the accuracy of calculating theglucose level. When a picture is taken of the eye, the calculated phaseangle and amplitude values may be compared to those of the strips. Inparticular, the strips will give amplitude and phase angles for very lowglucose values, thereby making extremely low glucose readings veryaccurate. There is visual confirmation of the amount of glucose on thestrips, which can be compared to the iris reflections. Both theamplitude and the phase angle are actual (not deduced), therebyeliminating error, and providing quality control, and enabling selfchecking.

It will be appreciated by those of skill in the art that one can alsoconstruct custom silicon arrays (e.g., a CCD) containing optimizingqualities to enhance spectral response for glucose detection. CCDs andcustom silicon arrays can be specially processed, modified, or enhancedto heighten their sensitivities to x-rays and other high energyparticles. In this case, the noninvasive measurement system may processx-rays or other high energy particles, instead of light waves. Moreover,CCDs and custom silicon arrays can be specially processed, modified, orenhanced to be made sensitive to ultraviolet rays to highlight or detectdifferent types of minerals.

It will be appreciated by those of skill in the art that the noninvasivemeasurement system may also be used to locate tumors and to locate andcorrect blood clots. In particular, a photo-multiplier can be placed infront of a CCD to enhance its sensitivity. Then, a high intensity lightthat is synchronized to the integration time of the CCD is used to sendlight through an individual. The amount of light in that high intensitylight source can penetrate flesh. For example, the noninvasivemeasurement system may be used to detect breast cancer.

Next, the noninvasive measurement system may apply a spatial filterafter taking the picture. The spatial filter, when used in the low-passmode, reduces unwanted image features that tend to show-up as highfrequency components. That is, the spatial filter takes out portions ofan image that create “noise” from non-glucose information. The filterparameters used operates on a 3×3 pixel area. The filter will take agroup of pixels (e.g., 9 pixels), average the values of the pixels, andset the values of each of the pixels in the group to that value. Forexample, if 2 of the 9 pixels are lit (i.e., set to one), and theremaining 7 pixels are not lit (i.e., set to zero), the average is zeroand all of the 9 pixels are set to zero. For example, tissue in the eyemay show up as high frequency, so the low pass filter will remove thesecomponents from the image array. A high pass filter will exaggeratethese components in the image array. The “hi-passed” data can beprocessed to uniquely identify an individual person. This can be used asan “iris fingerprint” to identify individuals by the uniquecharacteristics of their iris. The individual eye images can thus beautomatically correlated to specific patients.

The noninvasive measurement system may then perform automatic levelcontrol. Automatic level control attempts to ensure that the average ofall of the pixels is equivalent to the average of a calibrated average(i.e., an average that correlates to the calibrated data or desiredaverage). In one embodiment, the value 35 was found by experimentationto be the best value.

The camera and A/D converter returns the proper amplitudes for glucosedetection around this average. The number will be different for othercameras and converters. For example, if the data number is 35, then, theautomatic level control will find the average of the pixels. If theaverage is lower than the average data number (e.g., 35), the automaticlevel control adds 1 to each pixel. If the average is higher than thedata number (e.g., 35), the automatic level control subtracts 1 fromeach pixel. After the addition or subtraction process, the automaticlevel control finds a new average. If the new average is at or about 35,the automatic level control is complete. Otherwise, the automatic levelcontrol continues to add or subtract 1 to each pixel and calculating anew average until the new average is at or about 35.

The noninvasive measurement system calculates a true GRU or trueamplitude. The true GRU is the amplitude, with the phase angle portionremoved. In particular, the noninvasive measurement system calculatesthe true GRU as The GRU value—phase angle value. As will be discussedbelow, this amplitude is matched with the amplitude in thePhase/Amplitude lookup table to obtain the closest amplitude.

In one embodiment, if the phase angle (i.e., the XGRU and YGRU ratio) isfound to be an exact match a phase angle in the Phase/Amplitude lookuptable, the invention selects that phase angle and amplitude, and thecorresponding GLU value, without performing automatic fine tuning. Ifthere is no exact match, automatic fine tuning is performed.

In another embodiment, because it is rare to find an exact match,automatic fine tuning is always performed, without the initial check.Automatic fine involves tuning the Image matrix. The invention attemptsto get a close match between the phase angle found with the Image matrixand the phase angles available for comparison in the Phase/Amplitudelookup table. For example, if the phase angle is found by the XGRU andYGRU ratio to be 14020000, the invention attempts to fine tune the valueto reach either 14017754 (i.e., node 13 in the Phase/Amplitude lookuptable) or 14047686 (i.e., node 14 in the Phase/Amplitude lookup table).

The automatic fine tuning uses a Ternary technique. With the Ternarytechnique, if ¼ is to be added to the image matrix, 1 is added to eachfourth pixel. Then, a new phase angle is calculated. This phase angle isrecorded. This is done for 18 passes, with an amount being added each ofthe 18 times (e.g., 0.1 may be added for the first pass, another 0.1 isadded for the second pass, etc.). In each of the 18 passes, a value isadded to the pixels in the image matrix, then the phase angle iscalculated, then a close match is sought in the Phase/Amplitude lookuptable. This results in a FRC value that corresponds to the selectedentry in the Phase/Amplitude lookup table. Next, the FRC value is usedas an index into the Cousins table. Then, a comparison-is made betweenthe phase angle calculated in the pass and the phase angle for each ofthe cousins and the selected FRC. The FRC whose phase angle is closes tothe calculated phase angle is saved in an array, along with phase angleerror (MNP) and amplitude error (MNA). This array results in 18 valuescorresponding to the 18 passes. A mean phase angle is calculated fromthe 18 recorded values. This is then compared to the Phase/Amplitudelookup table to find a matching phase angle, amplitude, andcorresponding GLU. Also, the GLU value is used to index into the Cousinstable. The 18 passes are performed for each of four frame cousins(FRCs). The result is four final values and one is selected from thesefour.

For each of the 18 steps, start with frame cousin (FRC) 13, which has aGLU value of 136. FRC 13 is used because the GLU value 136 is near themiddle of the range. Also. FRC 13 has 8 cousins (the most cousinspossible in the Cousins table). Then, a comparison is made between thephase angle and the phase angle in the Phase/Amplitude lookup table foreach cousin. During the process, one of the cousins is identified asbeing closest to 136 by the phase angle. This results in 18 values foreach cousin within the FRC. Then, the FRC that is most often closest tothe image phase angle is chosen. In one embodiment, there are fouriterations, one starting with FRC 13, the next with FRC 14, the nextwith FRC 15, and the last starting with FRC 16. These frame cousinscover many comparisons because of the number of cousins that they have.Of the four results, the closest match to the Phase/Amplitude lookuptable is the selected answer. This answer is displayed, for example, ona monitor connected to a computer.

The focus is on the phase angle and not the amplitude because theamplitude is susceptible to environmental factors. Then, the finalresult is the GLU whose phase angle and amplitude most closely match anentry in the Phase/Amplitude lookup table.

The following pseudo-code reflects the processing performed by thenoninvasive measurement system. Some of the steps occur when particularcontrols are set on a control panel. These controls will be discussedbelow.

-   -   1. image the eyeball, with center brightness    -   2. adjust geometry of image to 640×480 pixels to match screen        size of personal computer (PC)    -   3. if programmable level bias is set (in the range of 0-255),        perform level bias on image    -   4. if gamma stretch set, perform gamma stretch (i.e., to produce        a non-linear stretch) (normally set for eye measurements, and is        set for skin measurements)    -   5. if pre-stretch set, perform first linear stretch    -   6. create pupil mask in identified shape (i.e., “L” shape or        rectangular shape)    -   7. corner tab cutter (zero out boxes in corners to remove        extraneous light, etc.)    -   8. if first filter set, use programmable low or high pass        filter, whichever is selected    -   9. if set, find center    -   10. if second filter set, use programmable low or high pass        filter, whichever is selected    -   11. if stretch set, control stretch from front panel (i.e., user        interface)    -   12. if image rotator set (i.e., can be used instead of Ternary        technique), rotate image    -   13. if automatic level control set, perform automatic level        control    -   14. if manual fine tuning set, perform manual fine tuning (i.e.,        Ternary technique for biasing image)    -   15. if automatic fine tuning set, perform automatic fine tuning        (i.e., Ternary weights are added in here)    -   16. if bitmap image format set, change format to an x-y image        format (i.e., an x-y array), which removes the bitmap header,        etc.

17. calculate GRU (i.e., by summing up all x rows and y columns in theCCD array)

-   -   18. convert image from 680×480 to 480×480    -   19. using 380 pixels (avoid using edges as it affects data, with        offset 50 pixels in from edge in each axis, leaving a black        margin at edge), sum up x axis and y axis and divide largest by        smallest to get value that is greater than one    -   20. obtain row information YPA (summation of rows); column YPB        (summation of columns) by calculating the following:

${{true}\mspace{14mu}{phase}\mspace{14mu}{angle}} = {\frac{{YPA} - ( {{YPA} - {YPB}} )}{{YPB} - ( {{YPB} - {YPA}} )} \times 10\mspace{14mu}{MILLION}}$true GRU/amplitude=GRU−(YPA+YPB)

-   -   21. perform automatic fine tuning, with 18 passes for each of 4        FRC values    -   22. select best true phase angle and true amplitude match    -   23. display results

D.2 Controls and Tables

FIG. 16 illustrates a control panel 1600 for one embodiment of theinvention. The Phase/Amplitude look up tables 1602 and 1604 have beencalibrated for different options. The Phase/Amplitude look up tables1602 is a LOW NODES ALC HP, which means that it was calibrated for lowbrightness (LOW NODES), using a automatic level control (ALC), and ahigh pass filter (HP). The Phase/Amplitude look up tables 1604 is LOWNODES, which means that it was calibrated for low brightness (LOWNODES). The RESTORE L control enables restoring a Phase/Amplitude lookup table with a large base table. A base table is a Phase/Amplitudetable, with large indicating it has the full range of glucose levels andsmall indicating it does not have the full range of glucose levels. TheRESTORE S control enables restoring a Phase/Amplitude look up table witha small base table. The AMPL TBL control displays an index, (e.g., 15),and a value corresponding to that index. The PHASE TBL control displaysan index and a value corresponding to that index.

The TAPA histogram 1606 displays the total energy of the incomingsource. The bar 1608 indicates the processing of the FRC values. The MXDATA histogram 1610 has an x-axis that goes from 1-450 milligrams anddisplays a statistical distribution of findings of 1-18 steps. The MXHDcontrol displays the data of an array that holds the 4 FRC values. ThePEAK control displays the peak value from the histogram 1610. The RESDcontrol displays the four glucose levels that correspond to the four FRCvalues selected with the auto fine tuning. The RES control displays theglucose level of the last FRC processed. The AVD control displays theaverage mg/dl value for each of the 4 FRC steps. The AVX controldisplays the average amplitude. The MNX control displays the minimumamplitude. The MAX control displays the maximum amplitude. The 2CYL/1CYLcontrol enables switching between 1 or 2 cycles. The PAUSE controlenables pausing the processing. The PHASE AT MATCH control displays thephase angle selected by the matching.

The error controls T1-T5 are lit upon the occurrence of certain errorconditions. The T1 control is lit when the phase code is too low. The T2control is lit when AVX and MNX are the same (i.e., these are theaverage and minimum amplitudes). The T3 control is lit when MX and MNare the same (i.e., these are the minimum and maximum glucose levelsthat are found). The T4 control is lit when MXAMP and MNAMP are thesame. The T5 Control is lit when the phase code is out of bounds.

Moving back to the top of the control panel, the PTWEEK control is aphase tweek that enables forcing the phase angle value to a particularvalue. The ATWEEK control is an amplitude tweek that enables forcing theamplitude value to a particular value. For a first filter, the FILTER1control enables setting no filter, a low pass filter, or a high passfilter. For a second filter, the FILTER2 control enables setting nofilter, a low pass filter, or a high pass filter. The FULL/PART controlselects the portion of the Phase/Amplitude table to be used in thelook-up process. FULL permits a look-up from FRC 0-37 and PART permits alook-up from FRC 10-18.

The XPOS control provides a readout of the X position of the mouse on animage, and the YPOS control provides a readout of the Y position of thecursor on an image. Together, the XPOS and YPOS enable selection of aparticular pixel. The DN control displays the data number of the pixellocated under the cursor. The DELTA control shows the difference betweenthe line or row image segment sums between the A and B frame. These arethe cumulative values of the pixels shown in the 2 waveform charts shownin FIG. 11.

The PUPL/NORM control is not used. The A-B/NORM control subtracts twoimages (e.g., Frame A-Frame B). The SIG Control is an edge detectionfilter, which is a version of a high-pass filter. The FLIP/PHASE controlenables inverting a phase angle. The ITER control displays an iterationof the 18 passes. The PHASE A and PHASE B controls are ratios for twoimages, Image A and Image B, respectively. The SUGAR control displays aglucose level. The ERROR A control is lit when an error occurs. When theERROR A control is lit, the SUGAR display is blanked out.

Moving to the graph on the right side, the A LINES graph 1612 displayseither the summation of the X values or the summation of the Y valuesfrom the CCD matrix, depending on which is selected with the SMX/SMYcontrol, for Image A.

The NEG control is lit red when the second frame (e.g., for Image B) hasa smaller GRU than the GRU of the first frame (e.g., for Image A). TheSTR control turns on a primary linear stretch. The COL control showsfalse color or black/white for the images that are displayed. The BALcontrol balances based on the geography of a pupil if there are few irispixels to work with (e.g., pupil too big). The A/B control enablesworking with two channels (i.e., two images) at once. The BIW controlenables, for all charts, either a black background or a whitebackground.

The CLN Control enables cloning the Image B file name to the Image Afile name to speed up manual processing. This avoids manually typing theinformation. The ALC control sets automatic level control. The INPcontrol displays the input image, rather than a processed image. The 3Dcontrol is used to select a 3D display format for false light intensitymaps. The PS control is a prestretch (before any other processingoccurs). The PCUT control sets a pupil cutter. The CAL control is on forcalibration of a pupil for a linear stretch.

The TABS control sets 4 corner tab masks. The LPAT control enablesselecting a square or L-shaped mask for the pupil. The BOX control isused to box in part of an image. The AMP/PHS control is used to selecteither amplitude or phase angle for indexing into the Phase/Amplitudetable when a best possible match is being sought. The STOP control stopsthe program. The SNAP control invokes another program to snap a pictureof the screen and store it as a bitmap. The SAVE control directly savesthe image displayed as a bitmap. The NODES DBL control can change theHI/LOW control, which selects a high brightness or low brightnessPhase/Amplitude lookup table, to select two other tables. The DLTAcontrol causes comparisons to be made where the final result is selectedbased on the same comparison polarity. If the incoming phase angle ishigher than the nearest table entry and the amplitude is lower than it'stable entry, the comparison will be rejected. The POL control is forpolarity. In particular, during comparison of values in thePhase/Amplitude lookup table, if BI is set, the answer can be above orbelow the actual value, and if MON is set, the value is the lower valuefound. The B LINES graph 1614 displays either the summation of the Xvalues or the summation of the Y values from the image matrix, dependingon which is selected with The SMX/SMY control, for Image B.

The PATH A and FILENAME A provide the path and filename used to locatethe storage location of Image A. The PATH B and FILENAME B provide thepath and filename used to locate the storage location of Image B. TheGAMA control is a gamma stretch control. The F MODE control enablesmanipulating the filter scope mode.

Moving back to the center of the control panel, there are several PHASEDIF controls. The B-A control is the phase angle difference between theA and B image channels. The T-A control shows the difference between theincoming phase angle and the table phase angle as indexed by the currentamplitude match. The PPSN control show the best FRC match based on thebest phase angle match found during a cousin table scan. The APSNcontrol shows the best FRC match based on the best amplitude match foundduring a cousin table scan. The AMPL control shows the differencebetween the incoming amplitude and the table amplitude as indexed by thecurrent amplitude match. The MNP control displays the phase angle error.The MNA control displays the amplitude error.

The TGRUA control displays the true GRU for Image A. The TGRUB controldisplays the true GRU for Image B. The T B-A control displays thedifference in true GRU between the A and B image channels. The MXAMPcontrol displays the maximum amplitude, the MNAMP control displays theminimum amplitude. The MX control shows the maximum GLU value. The MNcontrol shows the minimum GLU value. The UFM control displays theaverage before a filter is applied. The ERD control, is set, will setthe ERROR A control if any error indicator T1-T5 are on. The PUFMIcontrol displays the average before ALC is applied. The AV controldisplays the average of MX and MN. The CSN control indicates whether theCSN table (i.e., the cousins table) should be used or the primary FRCvalue should be used for comparisons. The 10X control indicates how muchshould be added to the CCD array in each of the 18 passes. The AUTO TUNEcontrol allows for selecting either pre-matrix (i.e., a sweep ofamplitude before decoding phase angle and amplitude) or post-matrix(i.e., a sweep of amplitude after decoding phase angle and amplitude).The MNPD control holds the MNP values. The MNAD control holds the MNAvalues.

Moving back to the top, the IMAGE control enables using the inputpicture exactly as it is or normalizing the picture to be 480×680. TheLINE/FRAME control enables capturing a line or a frame. The YPA controldisplays the XGRU. The YPB control displays the YGRU. The SEQ controlenables selection of the number of FRC values to process with 18 passes,and this can range from 0-37. The FRC control enables selection of theFRC value to start with. The FINE GAIN control is manual fine tuning,which forces an offset with a Tenary gain. The PUPIL BIAS control is apupil size compensator. The WINDOW LO and WINDOW HI controls enableselection of a low and high value, respectively, between 0-255; theresult of this is that specific pixels in the range are selected forprocessing.

The LOS control sets a low limit on a secondary stretch, and the HIScontrol sets a high limit on a secondary stretch. The LOP control sets alow limit on a primary stretch, and the HIP control sets a high limit onthe primary stretch. The OFFSET A control puts a numerical offset to theentire Image A, the OFFSET B control puts a numerical offset to theentire Image B. The BIAS A control enables adding to the computed pupilaverage of Image A. and the BIAS B control enables adding to the pupilaverage of Image B.

The ROT control is used to rotate the image. The MEAN A control displaysthe mean of Image A, while the DEV A control displays the standarddeviation. The MEAN B control displays the mean of Image B, while theDEV B control displays the standard deviation. The GRU A controldisplays the GRU of Image A, while the GRU B control displays the GRUfor Image B. The B-A control the raw GRU difference between image A andimage B. The PUPIL A control displays the brightness (before average) ofthe pupil of Image A. The PUPIL B control displays the brightness(before average) of the pupil of Image B. The threshold controlindicates at what value the GRU should be summed to. The GLIM controlindicates at what value the system should not sum after. The LEVEL Acontrol is average pupil brightness of image A, and the LEVEL B controlis the average pupil brightness of image B.

FIG. 17 displays another control panel 1700 for one embodiment of theinvention. This control panel displays a cousins table 1702. The cousinstable has a column for a FRC number (frame cousin), a glucose level(MG/DL), an amplitude (AMPL), a phase angle (PHASE), and columns foreight cousins. The cousins were derived using the NODE TABLE DATA graph1704. The NODE TABLE DATA graph is a graph of phase angle versusamplitude. The top line 1706 in the graph plots the ratio of phase angleto amplitude. The middle line 1708 plots amplitude, and the bottom line1710 plots phase angle. The cousin nodes in the Cousin table 1702 arenodes that are at approximately the same horizontal axis on the plot ofthe ratio. For example, for FRC 10, the cousins are FRC 25, FRC 28, FRC23, FRC 29, and FRC 18. Each of these frame cousins has a similar phaseangle to amplitude ratio.

FIG. 18 is illustrates various Phase/Amplitude lookup tables that havebeen calibrated for different settings. For example, in the LOW NODESALC table, LOW NODES refers to low brightness and ALC indicates thatautomatic level control was used. HIGH NODES indicates that there washigh brightness. The BASE refers to a base line table that wascalibrated with either a SMALL range of values or a LARGE (or all) rangeof values. DOUBLE FILTER indicates that two filters were set. COUSINSindicates that the cousins table was used.

FIG. 19 displays histograms for Image A and Image B. The A1 histogram1900 reflects Image A after a low pass filter has been applied. The A2histogram 1902 reflects Image A before the low pass filter. The A3histogram 1904 reflects Image A after a gamma stretch (If enabled). TheB1 histogram 1906 reflects Image B after a low pass filter has beenapplied. The B2 histogram 1908 reflects Image B before the low passfilter. The B3 histogram 1910 reflects Image B after a gamma stretch (Ifenabled).

D.3 Flow Diagram and Alternative Embodiments

FIGS. 20A-20C are a flow diagram illustrating the steps performed by thenoninvasive measurement system in one embodiment of the invention. Inblock 2000, the noninvasive measurement system images the eyeball, withcenter brightness. In block 2002, the noninvasive measurement systemadjusts the geometry of the image to 640×480 pixels to match a screensize of a personal computer(PC). In block 2004, if programmable levelbias is set (in the range of 0-255), the noninvasive measurement systemperforms level bias on the image. In block 2006, if gamma stretch isset, the noninvasive measurement system performs gamma stretch (i.e., ato produce a non-linear stretch). The gamma stretch is normally not setfor eye measurements, and is set for skin measurements.

In block 2008, if pre-stretch set, the noninvasive measurement systemperforms a first linear stretch. In block 2010, the noninvasivemeasurement system creates a pupil mask in a specified shape. In oneembodiment, a user may select either a “L” shape or a square shape. Inother embodiments, an oval or circular shape may be provided, but it mayrequire additional processing resources. In block 2012, corner tabcutter (zero out boxes in corners to remove extraneous light, etc.). Inblock 2014, if first filter set, the noninvasive measurement system useseither a programmable low or high pass filter, whichever is selected. Inblock 2016, if centering is set, the noninvasive measurement systemfinds the center. In block 2018, if second filter set, the noninvasivemeasurement system uses a programmable low or high pass filter,whichever is selected. In block 2020, if stretch set, the noninvasivemeasurement system controls stretch from input from the control panel.In block 2022, if image rotator is set, the noninvasive measurementsystem rotates the image (i.e., this can be used instead of Tenarytechnique).

In block 2024, if automatic level control is set, the noninvasivemeasurement system performs automatic level control. In block 2026, ifmanual fine tuning is set, the noninvasive measurement system performsmanual fine tuning (i.e., Ternary technique for biasing image). In block2028, if automatic fine tuning is set, the noninvasive measurementsystem performs automatic fine tuning (i.e., Ternary weights are addedin here). In block 2030, if bitmap image format is set, the noninvasivemeasurement system changes format to an x-y image format (i.e., an x-yarray), which removes the bitmap header, etc.

In block 2032, the noninvasive measurement system calculates GRU (i.e.,by summing up all x rows and y columns in the image array). In block2034, the noninvasive measurement system converts the image from 680×480to 480×480 pixels. In block 2036, using 380 pixels (i.e., thenoninvasive measurement system avoids using edges as it affects data, byoffsetting 50 pixels in from edge in each axis, leaving a black marginat edge), the noninvasive measurement system sums up the x rows and ycolumns and divides the largest by the smallest to get a value that isgreater than one. In block 2038, the noninvasive measurement systemobtains row information YPA (summation of rows) and column informationYPB (summation of columns) by calculating the following:

${{true}\mspace{14mu}{phase}\mspace{14mu}{angle}} = {\frac{{YPA} - ( {{YPA} - {YPB}} )}{{YPB} - ( {{YPB} - {YPA}} )} \times 10\mspace{14mu}{MILLION}}$true GRU/amplitude=GRU−(YPA+YPB).

In block 2040, the noninvasive measurement system performs automaticfine tuning, with 18 passes for each of 4 FRC values. In block 2042, thenoninvasive measurement system selects best true phase angle and trueamplitude match. In block 2046, the noninvasive measurement systemdisplays results.

The embodiment of the invention described in section D may be modifiedwithout exceeding the scope of the invention. For example, the techniqueof the invention may be practiced in a networked environment, asdescribed with respect to FIG. 2.

E. Noninvasive Measurement of Glucose Concentration in Skin, Blood, andNail Beds

The noninvasive measurement system can also measure glucoseconcentrations from skin (e.g., wrist or stomach), blood (e.g., a dropof blood on a tissue), or nail beds. For each of these cases, thenoninvasive measurement system generally uses the technique described inSection D, in which a phase angle and amplitude are correlated to aglucose level.

When working with the skin, a lower light level is used (i.e., the eveabsorbs more light). In particular, experimentation was successfullyperformed by using the noninvasive measurement device to transmit lightwaves onto a portion of the wrist. The wrist contains numerous bloodvessels, which may contain glucose molecules that reflect the lightwaves. A CCD camera was used to receive the reflected light waves fromthe wrist and to form a matrix of pixels that represented the receivedlight waves. Next, the noninvasive measurement system applied a gamma 1stretch to the matrix of pixels. This refers to a logarithmic re-mappingtechnique that gives more contrast for lower level pixels (small pixelvalues) and less contrast for higher level pixels (large pixel values),resulting in better resolution in the lower end. The noninvasivemeasurement system then processed the “stretched” matrix of pixels toobtain a phase angle and amplitude. From the phase angle and amplitude,the noninvasive measurement system found a glucose level. It is to beunderstood that this process can be modified without exceeding the scopeof the invention. For example, the controls of FIG. 16 may be set sothat a pupil cutter is also applied prior to calculating the phase angleand amplitude.

Additional experimentation was successfully performed by using thenoninvasive measurement device to take a picture of a portion of thestomach. In particular, experimentation was successfully performed byusing the noninvasive measurement device to transmit light waves onto aportion of the stomach. The stomach contains numerous blood vessels,which may contain glucose molecules that reflect the light waves. A CCDcamera was used to receive the reflected light waves from the stomachand to form a matrix of pixels that represented the received lightwaves. When this was done, a gamma 3 stretch was applied. This refers toa gamma stretch with a more gradual effect and that gives more contrastfor lower level pixels (small pixel values) and less contrast for higherlevel pixels (large pixel values), resulting in better resolution in thelower end. The noninvasive measurement system then processed the“stretched” matrix of pixels to obtain a phase angle and amplitude. Fromthe phase angle and amplitude, the noninvasive measurement system founda glucose level. It is to be understood that this process can bemodified without exceeding the scope of the invention. For example, thecontrols of FIG. 16 may be set so that a pupil cutter is also appliedprior to calculating the phase angle and amplitude.

Furthermore, experiments were performed with noninvasive measurementdevice against blood drops. The blood drop was either on a tissue or ona test strip that had been used to run a test on a conventional (onetouch) glucose monitor. With the test strips, the blood drop spread froma center point and retreated at an edge, so there were two layers ofblood at the perimeter. With test strips, better values were derivedfrom testing the perimeter. The blood drop was tested as the skin was,in less light. In particular, experimentation was successfully performedby using the noninvasive measurement device to transmit light waves ontothe blood, which may contain glucose molecules that reflect the lightwaves. A CCD camera was used to receive the reflected light waves fromthe blood drop and to form a matrix of pixels that represented thereceived light waves. The noninvasive measurement system then processedthe matrix of pixels to obtain a phase angle and amplitude. From thephase angle and amplitude, the noninvasive measurement system found aglucose level. It is to be understood that this process can be modifiedwithout exceeding the scope of the invention. For example, the controlsof FIG. 16 may be set so that a pupil cutter is applied prior tocalculating the phase angle and amplitude.

Further experiments were performed with nail beds. In particular,experimentation was successfully performed by using the noninvasivemeasurement device to transmit light waves onto the blood, which maycontain glucose molecules that reflect the light waves. A CCD camera wasused to receive the reflected light waves from the blood drop and toform a matrix of pixels that represented the received light waves. Anexperimental mask was implemented to allow the program to “see” thetissue edge at the side of the fingernail. The noninvasive measurementsystem then processed the matrix of pixels to obtain a phase angle andamplitude. From the phase angle and amplitude, the noninvasivemeasurement system found a glucose level. That is, the portion of theimage that was not masked was processed into GRU values and monotonicbrightness gains were observed with increasing blood glucose. It is tobe understood that this process can be modified without exceeding thescope of the invention. For example, the controls of FIG. 16 may be setso that a pupil cutter is also applied prior to calculating the phaseangle and amplitude.

The above options for using the noninvasive measurement device areprovided for illustration only. The noninvasive measurement system mayalso be used on other portions of a body (e.g., on a leg). Furthermore,although the discussion has used human experimentation, the techniquesof the invention are applicable to other biological entities.

F. Conclusion

This concludes the description of an embodiment of the invention. Thefollowing describes some alternative embodiments for accomplishing thepresent invention. For example, any type of computer, such as amainframe, minicomputer, or personal computer, or computerconfiguration, such as a timesharing mainframe, local area network, orstandalone personal computer, could be used with the present invention.

The foregoing description of an embodiment of the invention has beenpresented for the purposes of illustration and description. It is notintended to be exhaustive or to limit the invention to the precise formdisclosed. Many modifications and variations are possible in light ofthe above teaching. It is intended that the scope of the invention belimited not by this detailed description, but rather only by the claimsappended hereto.

1. A method of correlating captured wave data to a substance in abiological entity, comprising: receiving wave data reflected from thebiological entity; forming a plurality of pixels based on the reflectedwave data; determining an amplitude for the reflected wave data based onthe plurality of pixels; determining a phase angle for the reflectedwave data based on the plurality of pixels; and identifying a glucoselevel in the biological entity based on the amplitude and phase angle.2. The method of claim 1, wherein the determination of the amplitudecomprises calculating an integrated value.
 3. The method of claim 1,wherein the biological entity is an eye.
 4. The method of claim 3,wherein the step of determining the amplitude comprises integrating aportion of the plurality of pixels to form an integrated value; and thestep of identifying the glucose level comprises correlating theamplitude and the phase angle to a glucose level in a look up table. 5.The method of claim 4, wherein the integrating step further comprises:forming a matrix with the plurality of pixels; and masking a portion ofthe matrix.
 6. An apparatus for correlating captured wave data to asubstance in a biological entity, comprising: means for receiving wavedata reflected from the biological entity; means for forming a pluralityof pixels based on the reflected wave data; means for determining anamplitude for the reflected wave data based on the plurality of pixels;means for determining a phase angle for the reflected wave data based onthe plurality of pixels; and means for identifying a glucose level inthe biological entity based on the amplitude and the phase angle.
 7. Theapparatus of claim 6, further comprising means for calculating anintegrated value to obtain the amplitude.
 8. The apparatus of claim 6,wherein the biological entity is an eye.
 9. The apparatus of claim 8,wherein the means for determining the amplitude comprises means forintegrating a portion of the plurality of pixels to form an integratedvalue; and wherein the means for identifying the glucose level comprisesmeans for correlating the amplitude and the phase angle to a glucoselevel in a look up table.
 10. The apparatus of claim 9, wherein themeans for integrating comprises: means for forming a matrix with theplurality of pixels; and means for masking a portion of the matrix. 11.An apparatus for correlating captured wave data to a substance in abiological entity, comprising: a memory comprising a plurality ofinstructions; and a processing system coupled to the memory andconfigured to execute the plurality of instructions to: receive datacorresponding with wave data reflected from the biological entity; forma plurality of pixels based on the reflected wave data; determine anamplitude for the reflected wave data based on the plurality of pixels;determine a phase angle for the reflected wave data based on theplurality of pixels; and identify a glucose level in the biologicalentity based on the amplitude and the phase angle.
 12. The apparatus ofclaim 11, wherein the processing system is further configured todetermine the amplitude by calculating an integrated value.
 13. Theapparatus of claim 11, wherein the processing system is furtherconfigured to: determine the amplitude by integrating a portion of theplurality of pixels to form an integrated value; and identify a glucoselevel by correlating the amplitude and the phase angle to a glucoselevel in a look up table.
 14. The apparatus of claim 13, wherein theprocessing system is further configured to: form a matrix with theplurality of pixels; and mask a portion of the matrix.
 15. The apparatusof claim 11, further comprising an image capture device coupled to theprocessing system, and the processing system is further configured toreceive the data corresponding with the reflected wave data through theimage capture device.